Article    Table of Contents                    Abstract of this article Free    Figures/Tables List    Articles citing this article  Services    Send comment/rapid response letter    Notify a friend about this article    Alert me when this article is cited    Add to Personal Archive    Download to Citation Manager    ACP Search                            Get Permissions  Google Scholar    Search for Related Content  PubMed Articles in PubMed by Author:    Aguero-Rosenfeld, M. E.    Dumler, J. S.    Related Articles in PubMed    PubMed Citation    PubMed

BRIEF COMMUNICATION

Human Granulocytic Ehrlichiosis: A Case Series from a Medical Center in New York State

Maria E. Aguero-Rosenfeld, MD; Harold W. Horowitz, MD; Gary P. Wormser, MD; Donna F. McKenna, RN, CANP; John Nowakowski, MD; Jose Munoz, MD; and J. Stephen Dumler, MD

1 December 1996 | Volume 125 Issue 11 | Pages 904-908

Background: Human granulocytic ehrlichiosis (HGE) is a newly described illness with few reports in the literature.

Objective: To describe the clinical and laboratory features of HGE.

Design: Case series.

Setting: Tertiary care facility in New York State.

Patients: 18 adult patients with HGE.

Measurements: Epidemiologic, clinical, and laboratory features; treatment; and outcome of patients with HGE.

Results: Patients presented with such symptoms as fever (94%) and myalgia or arthralgia (78%). Thirteen patients (71%) recalled being bitten by a tick before onset of symptoms. Leukopenia or thrombocytopenia was seen in 82% of patients, and abnormal liver enzyme levels were seen in 81%. Results of polymerase chain reaction were positive in 9 of 12 patients (75%); morulae were seen in 3 of 12 patients (25%); and the agent that causes HGE was cultured from 2 patients. All but one patient (94%) developed antibodies to Ehrlichia equi. Five patients (28%) were briefly hospitalized, and none died. All patients were successfully treated with doxycycline.

Conclusions: The illness associated with HGE in these patients from the northeastern United States was more mild than that originally described in reports of HGE in the midwestern United States.

---

Human granulocytic ehrlichiosis (HGE) was first described in 1994 by Bakken and colleagues [1] in 12 patients from the midwestern United States. This report was followed by a retrospective case study [2] of 41 patients from the same geographic area. The data from these studies and from isolated case reports from several locations in the northeastern United States have been the only descriptions of the clinical and laboratory manifestations of HGE to date [2-5]. We describe the clinical and laboratory findings of 18 patients who received a diagnosis of HGE in 1994 or 1995 at a medical center in a populous area in the suburbs of New York City.

Methods

Top Methods Results Discussion Author & Article Info References

Patients

Patients were evaluated at the Westchester County Medical Center in 1994 and 1995; one patient (patient 18) has been discussed in another report [6]. At the first visit, samples of blood were obtained for complete blood cell count, differential count, chemistry profile, buffy-coat smear for examination of morulae, polymerase chain reaction (PCR) assay for HGE, and serologic examination to test for presence of antibodies to Ehrlichia equi and E. chaffeensis. Blood samples were also collected during the first to sixth weeks of convalescence.

Laboratory Testing

Buffy-coat smears were stained with Wright stain, and at least 1000 granulocytes were microscopically examined for Ehrlichia morulae. The presence of antibodies was tested for by indirect immunofluorescent antibody assay using horse granulocytes infected with E. equi at an initial serum dilution of 1:80 as described elsewhere [1]. We tested for antibodies to E. chaffeensis by using immunofluorescent antibody assay with infected DH82 cells [1, 7]. Peripheral blood was tested by PCR using EDTA-anticoagulated blood and the primer pair GE9f/GE10r as described elsewhere [8]. Samples of EDTA-anticoagulated blood from two patients (patients 14 and 15) were inoculated into an HL-60 cell line for culturing as described elsewhere [9].

Statistical Analysis

The two-tailed Student t-test, Pearson correlation (SPS software, Chicago, Illinois), and two-tailed Fisher exact test (EPISTAT software, Richardson, Texas) were used for data analysis.

Results

Top Methods Results Discussion Author & Article Info References

Eighteen patients received a diagnosis of HGE (3 in 1994 and 15 in 1995) in the Westchester County Medical Center. Most of these patients (83%) presented between June and August, Sixteen patients resided in Westchester County, and 2 resided in Putnam County; these counties are contiguous and located slightly north of New York City.

Thirteen patients (72%) reported that they had been bitten by a tick: Four ticks were positively identified as Ixodes scapularis (three nymphs and one adult tick). The other nine patients who reported a tick bite described a tick whose appearance was compatible with that of I. scapularis.

Symptoms appeared an average of 5.5 days after patients received the tick bite (Table 1). Two patients, neither of whom recalled being bitten by a tick, described a rash that they characterized as erythematous, pruritic, localized, and smaller than 5 cm in diameter. The described rash was not visible when these patients first visited the medical center. Patients were evaluated an average of 4.7 days after onset of symptoms (median, 3 days [range, 1 to 15 days]). Five patients (28%) required hospitalization for an average of 5 days. One patient (patient 15) was briefly admitted to an intensive care unit. None of the 18 patients died.

View this table: [in this window] [in a new window]   Table 1. Demographic Characteristics, Chronology, Clinical Presentation, and Treatment of 18 Patients with Human Granulocytic Ehrlichiosis*

 

Laboratory test results frequently showed leukopenia or thrombocytopenia and abnormal liver enzyme levels (Table 2). Lymphopenia (defined as <1.5 x 10³ lymphocytes/mL) was seen in 8 of 13 (62%) patients, and neutropenia (defined as <2 x 10³ neutrophils/µL) was seen in 3 of 13 (23%). Lymphopenia was seen in 8 of 9 (89%) patients who presented with an illness that lasted 4 days or less and in none of 4 patients with an illness that lasted 5 days or longer (P = 0.006). Neutropenia was seen in 3 of 4 (75%) patients who had HGE for longer than 4 days but in only 1 of 9 (11%) patients who had the disease for 4 days or less (P = 0.05). Pearson correlation analysis showed that the initial neutrophil count was inversely related to the duration of symptoms before the first visit (r = –0.58[95% CI, –0.851 to –0.019];P = 0.038) and that the lymphocyte count was directly related to the duration of symptoms before the first visit (r = 0.543 [CI, –0.033 to 0.836]; P = 0.055). Patients who had HGE for longer than 4 days usually had atypical lymphocytosis of at least 10% of the differential count. No patients had elevated serum creatinine or blood urea nitrogen levels, and only one patient had a low hemoglobin level. Leukocyte and platelet counts returned to normal during observation in all patients who received treatment; these values generally returned to normal earlier than did liver enzyme levels.

View this table: [in this window] [in a new window]   Table 2. Laboratory Variables during Acute and Convalescent Phases of Human Granulocytic Ehrlichiosis*

 

Intracytoplasmic morulae were seen in 3 of 12 patients (25%). The frequency of infected granulocytes ranged from 0.3% to 6% Table 2, and morulae were mostly seen in neutrophils (patient 15 had morulae in eosinophils). The presence of morulae correlated with age: Three of 4 patients older than 50 years of age and 0 of 8 patients younger than 50 years of age had morulae that could be detected. Results of polymerase chain reaction assay for HGE were positive in 9 of 12 patients (75%). All but 1 patient developed antibodies to E. equi. Three patients showed antibodies to E. chaffeensis in convalescent-phase specimens that had a higher titer ( 2560) to E. equi. The HGE agent grew in the HL-60 cell line from the blood of 2 patients (patients 14 and 15) who presented with HGE in the autumn of 1995.

All 18 patients received doxycycline therapy, beginning an average of 13.2 days (median, 6 days [range, 1 to 78 days]) after the onset of symptoms (Table 1). Seven patients were initially treated with other antimicrobial agents. The therapy of 2 patients was changed from amoxicillin to doxycycline within 2 days of treatment. The other 4 patients, who were initially treated with amoxicillin, had recurrent fever or persistence of symptoms after 1 to 2 weeks of therapy; for these patients, therapy was changed to doxycycline. Symptoms resolved in all patients 24 to 48 hours after the start of treatment with doxycycline, which was administered for an average of 14.2 days (range, 1 to 21 days). No symptoms have been seen after follow-up as long as 1 year.

Discussion

Top Methods Results Discussion Author & Article Info References

We describe 18 adult patients with HGE from the northeastern United States. Symptoms in these patients developed an average of 5.5 days after a presumed or proven bite from an Ixodes tick and frequently included fever (body temperature >38.3 °C), arthralgia and myalgia, and headache. Compared with the patients from the midwestern United States studied by Bakken and colleagues [1, 2], our patients were significantly younger (mean age ±SD, 47 ± 16 years compared with 57 ± 20 years; P = 0.04) and presented with a milder illness based on clinical and laboratory evaluations. Compared with the patients in our study, more midwestern patients were hospitalized (54% of midwestern patients compared with 28% in our study) and died (5% of midwestern patients compared with 0% in our study). Differences in case referral or in the threshold for diagnostic testing may explain some of these disparities.

Although HGE has a nonspecific clinical presentation, abnormal results on certain routine laboratory tests considerably narrow the differential diagnosis. A diagnosis of Lyme disease may be considered in a patient with fever after a bite from I. scapularis, but cytopenia is extremely rare in that disease [10]. In contrast, approximately 80% of our patients with HGE had leukopenia or thrombocytopenia. The explanation for these abnormal hematologic values and for abnormal liver enzyme levels is not yet known. Leukopenia can be caused by lymphopenia or neutropenia, with lymphopenia in the early stages of infection, followed by lymphocytosis with atypical lymphocytes.

Among the methods for specifically diagnosing HGE, microscopic detection of morulae is the quickest; for our patients, however, this method lacked sensitivity. Morulae were seen in 3 of 12 patients (25%) in our series compared with 80% of the midwestern patients. Visualization of intragranulocytic inclusions is probably an indication of massive infection and has been described as a risk factor, along with older age, for more serious illness [2]. In our series, PCR was the most sensitive diagnostic test during the acute phase. Nine of 12 (75%) of our patients had positive PCR results compared with 43% in the midwestern series [2]. As suggested by Bakken and colleagues, the lower sensitivity may have been caused by poor preservation of specimens and conditions that were suboptimal for the PCR assay.

Another diagnostic approach that offers definitive evidence of infection is isolation of the organism in culture [9]. In our study, culture was done for two patients in whom morulae were seen in peripheral blood granulocytes; Ehrlichia was isolated in both cases. However, this technique is probably not easily done in most clinical laboratories, and its sensitivity has not yet been determined.

Detection of antibodies to E. equi by immunofluorescent antibody assay is useful for confirming the diagnosis of HGE, but often only in retrospect. During the acute phase of HGE, the results of immunofluorescent antibody assay were positive in only 29% of our patients and 23% of the patients in the midwestern cohort. Current serologic assays to detect antibodies to Ehrlichia, however, lack standardization. Although all but one patient (94%) in our series developed antibodies to E. equi, the sensitivity and specificity of serologic testing have not been defined. Because Bakken and colleagues [2] reported that E. equi antibodies persist for longer than 1 year in nearly 50% of persons with HGE, some background seroreactivity probably exists in highly endemic areas; this possibility should therefore be considered when patients are evaluated. Another potential source of diagnostic confusion is cross-reactivity between E. equi and E. chaffeensis (the agent of human monocytic ehrlichiosis). Three (17%) of our patients had antibodies to E. chaffeensis (2 in low titer) as did 3 (8%) of 40 midwestern patients [2] and another patient with HGE in Massachusetts who was described in another study [4]. The practitioner must be aware that human monocytic ehrlichiosis and HGE are caused by distinct pathogens and that distinct diagnostic tests must therefore be requested for diagnosis to be confirmed or excluded.

Patients with HGE respond clinically within 48 hours of treatment with tetracyclines; empirical treatment may thus be warranted when strong clinical suspicion exists. The optimal duration of therapy has not yet been established, but short courses may be as effective as longer ones. Because of intolerance to the drug, one of our patients received doxycycline for only 1 day, but clinical and laboratory evidence of infection nonetheless resolved. In the studies by Bakken and colleagues [1, 2], the symptoms of six (15%) patients completely resolved without specific treatment. Many cases of HGE may be subclinical and self-limiting, a phenomenon that has been well documented with human monocytic ehrlichiosis [11, 12]. Tetracyclines are also excellent therapy for early Lyme disease, which is particularly important when Lyme disease alone, or as a coinfection with HGE, cannot be excluded [13]. Our case series either represents a milder form of illness caused by the same pathogen that was described in the midwestern United States or reflects the clinical disease caused by a closely related organism that has different virulence properties. Only when diagnostic testing becomes more widely available and more reliable and when large patient samples are systematically studied will the true incidence and clinical spectrum of this potentially serious illness be understood.

Drs. Horowitz, Wormser, and Nowakowski: Division of Infectious Diseases, Westchester County Medical Center, Macy Pavilion 209 SE, Valhalla, NY 10595.

Ms. McKenna: Main Nursing Office, Westchester County Medical Center, Valhalla, NY 10595.

Dr. Munoz: New York Medical College, Department of Pediatrics, Munger Pavilion Room 113, Valhalla, NY 10595.

Dr. Dumler: Division of Medical Microbiology, Department of Pathology, Meyer B1-193, The Johns Hopkins Medical Institutions, 600 North Wolfe Street, Baltimore, MD 21287.

Author and Article Information

Top Methods Results Discussion Author & Article Info References

From New York Medical College and Westchester County Medical Center, Valhalla, New York; and The Johns Hopkins Medical Institutions, Baltimore, Maryland.
Note: The contents of this manuscript are solely the responsibility of the authors and do not represent the official views of the Centers for Disease Control and Prevention or the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Acknowledgments: The authors thank Eleanor Shields, Lois DeLungo, Odile Levrat, Olga McDermott, Kristin Asanovich, Jen Walls, and Dan Edelman for their excellent technical assistance and Dan Byrne for statistical analysis.
Grant Support: In part by Cooperative Agreement U50/CCU 210280 from the Centers for Disease Control and Prevention (Dr. Wormser), grants RO1-AR41508 (Drs. Nowakowski and Wormser) and RO1-AR43135 (Dr. Wormser) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, a Research Initiative Support Award by the University of Maryland School of Medicine, and Grant-in-Aid award BG2094 by the Maryland Chapter of the American Heart Association (Dr. Dumler).
Requests for Reprints: Maria E. Aguero-Rosenfeld, MD, Clinical Laboratories, Room 1J-11a, Westchester County Medical Center, Valhalla, NY 10595.
Current Author Addresses: Dr. Aguero-Rosenfeld: Clinical Laboratories, Room 1J-11a, Westchester County Medical Center, Valhalla, NY 10595.

References

Top Methods Results Discussion Author & Article Info References

1. Bakken JS, Dumler JS, Chen SM, Eckman MR, Van Etta LL, Walker DH. Human granulocytic ehrlichiosis in the upper Midwest United States. A new species emerging? JAMA. 1994; 272:212-8.

2. Bakken JS, Krueth J, Wilson-Nordskog C, Tilden RL, Asanovich K, Dumler JS. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA. 1996; 275:199-205.

3. Human granulocytic ehrlichiosis—New York, 1995. MMWR Morb Mortal Wkly Rep. 1995; 44:593-5.

4. Telford SR 3d, Lepore TJ, Snow P, Warner CK, Dawson JE. Human granulocytic ehrlichiosis in Massachusetts. Ann Intern Med. 1995; 123:277-9.[Free Full Text]

5. Hardalo CJ, Quagliarello V, Dumler JS. Human granulocytic ehrlichiosis in Connecticut: report of a fatal case. Clin Infect Dis. 1995; 21:910-4.

6. Horowitz HW, Marks SJ, Weintraub M, Dumler JS. Brachial plexopathy associated with human granulocytic ehrlichiosis. Neurology. 1996; 46:1026-8.

7. Dumler JS, Asanovich KM, Bakken JS, Richter P, Kimsey R, Madigan JE. Serologic cross-reactions among Ehrlichia equi, Ehrlichia phagocytophila, and human granulocytic. Ehrlichia. J Clin Microbiol. 1995; 33:1098-103.

8. Edelman DC, Dumler JS. Evaluation of an improved PCR diagnostic assay for human granulocytic ehrlichiosis. Molecular Diagnostics. 1996; 1:41-9.

9. Goodman, JL, Nelson C, Vitale B, Madigan JE, Dumler JS, Kurtti TJ, et al. Direct cultivation of the causative agent of human granulocytic ehrlichiosis. N Engl J Med. 1996; 334:209-15.[Abstract/Free Full Text]

10. Nadelman RB, Nowakowski J, Forseter G, Goldberg NS, Bittker S, Cooper D, et al. The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. Am J Med. 1996; 100:502-8.

11. Fishbein DB, Dawson JE, Robinson LE. Human ehrlichiosis in the United States, 1985 to 1990. Ann Intern Med. 1994; 120:736-43.

12. Petersen LR, Sawyer LA, Fishbein DB, Kelley PW, Thomas RJ, Magnarelli LA, et al. An outbreak of ehrlichiosis in members of an Army Reserve unit exposed to ticks. J Infect Dis. 1989; 159:562-8.

13. Wormser GP, Horowitz HW, Dumler JS, Schwartz I, Aguero-Rosenfeld M. False-positive Lyme disease serology in human granulocytic ehrlichiosis [Letter]. Lancet. 1996; 347:981-2.

This article has been cited by other articles:

				A. F. Barbet, A. M. Lundgren, A. R. Alleman, S. Stuen, A. Bjoersdorff, R. N. Brown, N. L. Drazenovich, and J. E. Foley Structure of the Expression Site Reveals Global Diversity in MSP2 (P44) Variants in Anaplasma phagocytophilum Infect. Immun., November 1, 2006; 74(11): 6429 - 6437. [Abstract] [Full Text] [PDF]

				A. Alberti, R. Zobba, B. Chessa, M. F. Addis, O. Sparagano, M. L. Pinna Parpaglia, T. Cubeddu, G. Pintori, and M. Pittau Equine and Canine Anaplasma phagocytophilum Strains Isolated on the Island of Sardinia (Italy) Are Phylogenetically Related to Pathogenic Strains from the United States Appl. Envir. Microbiol., October 1, 2005; 71(10): 6418 - 6422. [Abstract] [Full Text] [PDF]

				L. J. DEMMA, R. C. HOLMAN, J. H. MCQUISTON, J. W. KREBS, and D. L. SWERDLOW EPIDEMIOLOGY OF HUMAN EHRLICHIOSIS AND ANAPLASMOSIS IN THE UNITED STATES, 2001-2002 Am J Trop Med Hyg, August 1, 2005; 73(2): 400 - 409. [Abstract] [Full Text] [PDF]

				H. M. Heller, S. R. Telford III, and J. A. Branda Case 10-2005 - A 73-Year-Old Man with Weakness and Pain in the Legs N. Engl. J. Med., March 31, 2005; 352(13): 1358 - 1364. [Full Text] [PDF]

				M Bayard-Mc Neeley, A Bansal, I Chowdhury, G Girao, C B Small, K Seiter, J Nelson, D Liveris, I Schwartz, D F Mc Neeley, et al. In vivo and in vitro studies on Anaplasma phagocytophilum infection of the myeloid cells of a patient with chronic myelogenous leukaemia and human granulocytic ehrlichiosis J. Clin. Pathol., May 1, 2004; 57(5): 499 - 503. [Abstract] [Full Text] [PDF]

				J. A. Carlyon, M. Akkoyunlu, L. Xia, T. Yago, T. Wang, R. D. Cummings, R. P. McEver, and E. Fikrig Murine neutrophils require {alpha}1,3-fucosylation but not PSGL-1 for productive infection with Anaplasma phagocytophilum Blood, November 1, 2003; 102(9): 3387 - 3395. [Abstract] [Full Text] [PDF]

				T. Yago, A. Leppanen, J. A. Carlyon, M. Akkoyunlu, S. Karmakar, E. Fikrig, R. D. Cummings, and R. P. McEver Structurally Distinct Requirements for Binding of P-selectin Glycoprotein Ligand-1 and Sialyl Lewis x to Anaplasma phagocytophilum and P-selectin J. Biol. Chem., September 26, 2003; 278(39): 37987 - 37997. [Abstract] [Full Text] [PDF]

				P. J. Krause, C. L. Corrow, and J. S. Bakken Successful Treatment of Human Granulocytic Ehrlichiosis in Children Using Rifampin Pediatrics, September 1, 2003; 112(3): e252 - 253. [Abstract] [Full Text] [PDF]

				A. F. Barbet, P. F. M. Meeus, M. Belanger, M. V. Bowie, J. Yi, A. M. Lundgren, A. R. Alleman, S. J. Wong, F. K. Chu, U. G. Munderloh, et al. Expression of Multiple Outer Membrane Protein Sequence Variants from a Single Genomic Locus of Anaplasma phagocytophilum Infect. Immun., April 1, 2003; 71(4): 1706 - 1718. [Abstract] [Full Text]

				C. D. Paddock and J. E. Childs Ehrlichia chaffeensis: a Prototypical Emerging Pathogen Clin. Microbiol. Rev., January 1, 2003; 16(1): 37 - 64. [Abstract] [Full Text] [PDF]

				M. Maurin, J. S. Bakken, and J. S. Dumler Antibiotic Susceptibilities of Anaplasma (Ehrlichia) phagocytophilum Strains from Various Geographic Areas in the United States Antimicrob. Agents Chemother., January 1, 2003; 47(1): 413 - 415. [Abstract] [Full Text] [PDF]

				M. E. Aguero-Rosenfeld, L. Donnarumma, L. Zentmaier, J. Jacob, M. Frey, R. Noto, C. A. Carbonaro, and G. P. Wormser Seroprevalence of Antibodies That React with Anaplasma phagocytophila, the Agent of Human Granulocytic Ehrlichiosis, in Different Populations in Westchester County, New York J. Clin. Microbiol., July 1, 2002; 40(7): 2612 - 2615. [Abstract] [Full Text] [PDF]

				T. Avsic-Zupanc, M. Petrovec, W. L. Nicholson, J. W. Sumner, J. E. Childs, and F. Strle Clinical and Serological Follow-Up of Patients with Human Granulocytic Ehrlichiosis in Slovenia Clin. Vaccine Immunol., September 1, 2001; 8(5): 899 - 903. [Abstract] [Full Text] [PDF]

				M. Akkoyunlu, S. E. Malawista, J. Anguita, and E. Fikrig Exploitation of Interleukin-8-Induced Neutrophil Chemotaxis by the Agent of Human Granulocytic Ehrlichiosis Infect. Immun., September 1, 2001; 69(9): 5577 - 5588. [Abstract] [Full Text] [PDF]

				S. E. Carter, M. D. Ravyn, Y. Xu, and R. C. Johnson Molecular Typing of the Etiologic Agent of Human Granulocytic Ehrlichiosis J. Clin. Microbiol., September 1, 2001; 39(9): 3398 - 3401. [Abstract] [Full Text] [PDF]

				M. E. Martin, K. Caspersen, and J. S. Dumler Immunopathology and Ehrlichial Propagation Are Regulated by Interferon-{{gamma}} and Interleukin-10 in a Murine Model of Human Granulocytic Ehrlichiosis Am. J. Pathol., May 1, 2001; 158(5): 1881 - 1888. [Abstract] [Full Text] [PDF]

				H. W. Horowitz, T.-C. Hsieh, M. E. Aguero-Rosenfeld, F. Kalantarpour, I. Chowdhury, G. P. Wormser, and J. M. Wu Antimicrobial Susceptibility of Ehrlichia phagocytophila Antimicrob. Agents Chemother., March 1, 2001; 45(3): 786 - 788. [Abstract] [Full Text]

				N. A. Shadick, M. H. Liang, C. B. Phillips, K. Fossel, and K. M. Kuntz The Cost-effectiveness of Vaccination Against Lyme Disease Arch Intern Med, February 26, 2001; 161(4): 554 - 561. [Abstract] [Full Text] [PDF]

				M. D. Ravyn, C. B. Kodner, S. E. Carter, J. L. Jarnefeld, and R. C. Johnson Isolation of the Etiologic Agent of Human Granulocytic Ehrlichiosis from the White-Footed Mouse (Peromyscus leucopus) J. Clin. Microbiol., January 1, 2001; 39(1): 335 - 338. [Abstract] [Full Text]

				P. Caturegli, K. M. Asanovich, J. J. Walls, J. S. Bakken, J. E. Madigan, V. L. Popov, and J. S. Dumler ankA: an Ehrlichia phagocytophila Group Gene Encoding a Cytoplasmic Protein Antigen with Ankyrin Repeats Infect. Immun., September 1, 2000; 68(9): 5277 - 5283. [Abstract] [Full Text] [PDF]

				T. Tajima, N. Zhi, Q. Lin, Y. Rikihisa, H. W. Horowitz, J. Ralfalli, G. P. Wormser, and K. E. Hechemy Comparison of Two Recombinant Major Outer Membrane Proteins of the Human Granulocytic Ehrlichiosis Agent for Use in an Enzyme-Linked Immunosorbent Assay Clin. Vaccine Immunol., July 1, 2000; 7(4): 652 - 657. [Abstract] [Full Text] [PDF]

				F. Kalantarpour, I. Chowdhury, G. P. Wormser, and M. E. Aguero-Rosenfeld Survival of the Human Granulocytic Ehrlichiosis Agent under Refrigeration Conditions J. Clin. Microbiol., June 1, 2000; 38(6): 2398 - 2399. [Abstract] [Full Text]

				M. Akkoyunlu and E. Fikrig Gamma Interferon Dominates the Murine Cytokine Response to the Agent of Human Granulocytic Ehrlichiosis and Helps To Control the Degree of Early Rickettsemia Infect. Immun., April 1, 2000; 68(4): 1827 - 1833. [Abstract] [Full Text] [PDF]

				J.-s. Chae, J. E. Foley, J. S. Dumler, and J. E. Madigan Comparison of the Nucleotide Sequences of 16S rRNA, 444 Ep-ank, and groESL Heat Shock Operon Genes in Naturally Occurring Ehrlichia equi and Human Granulocytic Ehrlichiosis Agent Isolates from Northern California J. Clin. Microbiol., April 1, 2000; 38(4): 1364 - 1369. [Abstract] [Full Text]

				K. Yoshiie, H.-Y. Kim, J. Mott, and Y. Rikihisa Intracellular Infection by the Human Granulocytic Ehrlichiosis Agent Inhibits Human Neutrophil Apoptosis Infect. Immun., March 1, 2000; 68(3): 1125 - 1133. [Abstract] [Full Text] [PDF]

				M. E. Aguero-Rosenfeld, F. Kalantarpour, M. Baluch, H. W. Horowitz, D. F. McKenna, J. T. Raffalli, T.-c. Hsieh, J. Wu, J. S. Dumler, and G. P. Wormser Serology of Culture-Confirmed Cases of Human Granulocytic Ehrlichiosis J. Clin. Microbiol., February 1, 2000; 38(2): 635 - 638. [Abstract] [Full Text]

				J. J. Walls, P. Caturegli, J. S. Bakken, K. M. Asanovich, and J. S. Dumler Improved Sensitivity of PCR for Diagnosis of Human Granulocytic Ehrlichiosis Using epank1 Genes of Ehrlichia phagocytophila-Group Ehrlichiae J. Clin. Microbiol., January 1, 2000; 38(1): 354 - 356. [Abstract] [Full Text]

				J. J. Walls, M. Aguero-Rosenfeld, J. S. Bakken, J. L. Goodman, D. Hossain, R. C. Johnson, and J. S. Dumler Inter- and Intralaboratory Comparison of Ehrlichia equi and Human Granulocytic Ehrlichiosis (HGE) Agent Strains for Serodiagnosis of HGE by the Immunofluorescent-Antibody Test J. Clin. Microbiol., September 1, 1999; 37(9): 2968 - 2973. [Abstract] [Full Text]

				J. A. Comer, W. L. Nicholson, J. G. Olson, and J. E. Childs Serologic Testing for Human Granulocytic Ehrlichiosis at a National Referral Center J. Clin. Microbiol., March 1, 1999; 37(3): 558 - 564. [Abstract] [Full Text]

				J. J. Walls, K. M. Asanovich, J. S. Bakken, and J. S. Dumler Serologic Evidence of a Natural Infection of White-Tailed Deer with the Agent of Human Granulocytic Ehrlichiosis in Wisconsin and Maryland Clin. Vaccine Immunol., November 1, 1998; 5(6): 762 - 765. [Abstract] [Full Text]

				H.-Y. Kim and Y. Rikihisa Characterization of Monoclonal Antibodies to the 44-Kilodalton Major Outer Membrane Protein of the Human Granulocytic Ehrlichiosis Agent J. Clin. Microbiol., November 1, 1998; 36(11): 3278 - 3284. [Abstract] [Full Text]

				H. W. Horowitz, E. Kilchevsky, S. Haber, M. Aguero-Rosenfeld, R. Kranwinkel, E. K. James, S. J. Wong, F. Chu, D. Liveris, and I. Schwartz Perinatal Transmission of the Agent of Human Granulocytic Ehrlichiosis N. Engl. J. Med., August 6, 1998; 339(6): 375 - 378. [Full Text] [PDF]

				S. J. Wong and J. A. Thomas Cytoplasmic, Nuclear, and Platelet Autoantibodies in Human Granulocytic Ehrlichiosis Patients J. Clin. Microbiol., July 1, 1998; 36(7): 1959 - 1963. [Abstract] [Full Text]

				M. D. Ravyn, J. L. Goodman, C. B. Kodner, D. K. Westad, L. A. Coleman, S. M. Engstrom, C. M. Nelson, and R. C. Johnson Immunodiagnosis of Human Granulocytic Ehrlichiosis by Using Culture-Derived Human Isolates J. Clin. Microbiol., June 1, 1998; 36(6): 1480 - 1488. [Abstract] [Full Text]

				N. Zhi, N. Ohashi, Y. Rikihisa, H. W. Horowitz, G. P. Wormser, and K. Hechemy Cloning and Expression of the 44-Kilodalton Major Outer Membrane Protein Gene of the Human Granulocytic Ehrlichiosis Agent and Application of the Recombinant Protein to Serodiagnosis J. Clin. Microbiol., June 1, 1998; 36(6): 1666 - 1673. [Abstract] [Full Text]

				B. J. Wallace, G. Brady, D. M. Ackman, S. J. Wong, G. Jacquette, E. E. Lloyd, and G. S. Birkhead Human Granulocytic Ehrlichiosis in New York Arch Intern Med, April 13, 1998; 158(7): 769 - 773. [Abstract] [Full Text] [PDF]

				R. F. Massung, K. Slater, J. H. Owens, W. L. Nicholson, T. N. Mather, V. B. Solberg, and J. G. Olson Nested PCR Assay for Detection of Granulocytic Ehrlichiae J. Clin. Microbiol., April 1, 1998; 36(4): 1090 - 1095. [Abstract] [Full Text]

				H. W. Horowitz and G. P. Wormser Doxycycline Revisited: An Old Medicine for Emerging Diseases Arch Intern Med, January 26, 1998; 158(2): 192 - 193. [Full Text] [PDF]

				R. B. Nadelman, H. W. Horowitz, T.-c. Hsieh, J. M. Wu, M. E. Aguero-Rosenfeld, I. Schwartz, J. Nowakowski, S. Varde, and G. P. Wormser Simultaneous Human Granulocytic Ehrlichiosis and Lyme Borreliosis N. Engl. J. Med., July 3, 1997; 337(1): 27 - 30. [Full Text] [PDF]

Article    Table of Contents                    Abstract of this article Free    Figures/Tables List    Articles citing this article  Services    Send comment/rapid response letter    Notify a friend about this article    Alert me when this article is cited &n