Human Granulocytic Ehrlichiosis -- New York, 1995

Since 1986, two human tickborne diseases caused by Ehrlichia spp. have been recognized in the United States: human monocytic ehrlichiosis (HME), caused by E. chaffeensis, and human granulocytic ehrlichiosis (HGE), caused by an agent closely related to E. equi (1,2). In June 1995, the Westchester County (New York) Department of Health (WCDOH) received reports from physicians who were treating patients for suspected HGE. In response, the WCDOH sent information to all primary-care physicians in Westchester County describing the clinical and laboratory features of ehrlichiosis (fever, myalgia, headache, leukopenia, and thrombocytopenia) and requested that they voluntarily report suspected cases of ehrlichiosis. This report summarizes an investigation by the New York State Department of Health (NYSDOH) and the WCDOH of suspected ehrlichiosis cases and the clinical characteristics of confirmed and probable cases.

Hospitals and large group practices in Westchester County were asked to report current and past suspected cases, and the NYSDOH laboratory initiated free diagnostic testing for ehrlichiosis for New York state residents. Potential cases of ehrlichiosis were identified through reports submitted by health-care providers to their county health departments and from a review of NYSDOH laboratory records of serum specimens that were submitted for diagnostic testing for ehrlichiosis since 1994. Serum specimens from potential cases were tested for antibodies to E. equi and/or E. chaffeensis, and/or the presence of DNA of the HGE agent by polymerase chain reaction (PCR) assay. A confirmed case of HGE was defined as either a fourfold change in antibody titer to E. equi or identification of DNA sequences of the HGE agent by PCR assay. A probable case of HGE was defined as a single antibody titer greater than or equal to 64 by immunofluorescent assay to E. equi or the identification of organisms (morulae) in granulocytes on a peripheral blood smear from a patient with an acute illness characterized by fever, headache, myalgia, and/or malaise.

As of August 15, 1995, medical records and/or clinical information had been reviewed for 68 patients with suspected ehrlichiosis: 50 had onset in 1995; 17, in 1994; and one, in 1992. Serum specimens from 30 patients had been tested for antibodies to E. equi and/or E. chaffeensis; 20 patients had acute serum specimens tested by PCR analysis.

Illnesses in 29 patients met the case definition of either confirmed (23 patients) or probable (six patients) HGE, 20 from 1995 and nine from 1994; other potential cases remain under investigation. Eighteen (62%) case-patients had onset of symptoms in June or July 1995. Twenty-five patients lived in Westchester County, two lived north of Westchester in adjacent Putnam County, and two lived on Long Island in Nassau and Suffolk counties. The mean age of patients with confirmed or probable HGE was 49 years (range: 21-90 years), and 15 (52%) were male. Fourteen (48%) of the 29 case-patients reported a tick bite less than or equal to 21 days before onset of illness. Fever greater than 101.0 F ( greater than 38.3 C) was noted in 27 patients. Reported symptoms included headache (22 patients), arthralgia (13), malaise (11), and myalgia (11). The lowest reported platelet count for 21 patients averaged 106,000 mm3 (range: 28,000-275,000 mm3; normal: 150,000-350,000 mm3), and the lowest reported white blood cell count for 26 patients averaged 4200 mm3 (range: 700-7700 mm3; normal: 4300-10,800 mm3). Thirteen patients had mild serum elevations of liver enzymes aspartase aminotransferase, alanine aminotransferase, and lactate dehydrogenase. Thirteen patients were hospitalized, and none died. Twenty-two patients received doxycycline during their acute illness.

Of the 23 confirmed cases, 11 had a fourfold rise in antibody titer to E. equi using a polyvalent antihuman conjugate, and 15 had HGE 16S ribosomal DNA detected from acute serum specimens (a positive PCR test). One confirmed case also had characteristic morulae observed in granulocytes on a peripheral blood smear. The six probable cases had single titers greater than or equal to 64 to E. equi. Five case-patients had serologic evidence of E. chaffeensis infection (titer greater than or equal to 64) but all had at least a 10-fold greater titer to E. equi. Reported by: G Wormser, MD, D McKenna, M Aguero-Rosenfeld, MD, H Horowitz, MD, J Munoz, MD, J Nowakowski, MD, G Gerina, MD, Westchester County Medical Center, Valhalla; P Welch, MD, Mt. Kisco; H Moorjani, MD, T Rush, MD, Tarrytown; G Jacquette, MD, A Stankey, R Falco, PhD, M Rapoport, MD, Westchester County Dept of Health, Hawthorne; D Ackman, MD, J Talarico, DO, D White, PhD, L Friedlander, R Gallo, G Brady, M Mauer, DO, S Wong, PhD, R Duncan, L Kingsley, R Taylor, G Birkhead, MD, D Morse, MD, State Epidemiologist, New York State Dept of Health. JS Dumler, MD, Univ of Maryland Medical Center, Baltimore, Maryland. Viral and Rickettsial Zoonoses Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: HGE was first described in 1994 among patients in Minnesota and Wisconsin. In addition to these cases, reports have suggested that acquisition of HGE may have occurred in California, Florida, Maryland, Massachusetts, and New York (4,5). Approximately 400 cases of HME have been confirmed in 30 states, primarily in the southeastern and south central regions (3). E. chaffeensis has most commonly been identified in the Lone Star tick (Amblyomma americanum), while HGE has been identified in the deer (Ixodes scapularis) and dog (Dermacentor variabilis) ticks (2).

Physicians evaluating patients with an acute febrile illness should consider ehrlichiosis in the differential diagnosis, particularly if the patient is leukopenic or thrombocytopenic, and should solicit a history of known or possible exposure to ticks. Empiric therapy with doxycycline antibiotics should be considered if the diagnosis of ehrlichiosis is suspected because delayed treatment while awaiting laboratory confirmation may increase the risk for adverse outcomes. The diagnosis can be confirmed through antibody assays and/or PCR. The agent that causes HGE has not been identified in cell culture, but tests for antibody to E. equi have been used to confirm the diagnosis. The sensitivity, specificity, and cross-reactivity of serologic assays for the two species are not well established. Because the geographic distribution of HME and HGE overlap, physicians should consider obtaining serologic tests for both E. equi and E. chaffeensis. PCR is a useful research tool but is not widely available for diagnostic purposes.

The patients described in this report live in areas where I. scapularis is common. I. scapularis collected in Westchester and Suffolk counties have been found positive for the HGE agent by PCR assay (CDC, unpublished data, 1995). The geographic extent of HGE in New York is not known. Persons spending time outdoors in tick-infested areas should take precautions against tickborne diseases, including wearing light-colored clothing, using insect repellent, and checking thoroughly for ticks after being outdoors. The NYSDOH has asked physicians in New York to report suspected cases to their local health departments. In addition, the NYSDOH is working with local health departments to provide information to the public and medical community and is offering serologic testing for HME and HGE through the NYSDOH laboratory. CDC provides serologic and PCR testing for HME and HGE of specimens sent through state health departments.

References

1. Dawson JE, Anderson BE, Fishbein DB, et al. Isolation and characterization of and Ehrlichia sp. from a patient diagnosed with human ehrlichiosis. J Clin Microbiol 1991;29:2741-5.

2. Bakken JS, Dumler JS, Chen SM, Eckman MR, Van Etta LL, Walker DH. Human granulocytic ehrlichiosis in the upper midwest United States. JAMA 1994;272:212-8.

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

4. Dumler JS, Bakken JS. Ehrlichial diseases of humans: emerging tick-borne infections. Clin Infect Dis 1995;20:1102-10.

5. Telford SR, Lepore TJ, Snow P, Warner CK, Dawson JE. Human granulocytic ehrlichiosis in Massachusetts. Ann Intern Med 1995;123:277-9.

+------------------------------------------------------------------- ---+ |             | | Errata: Vol. 44, No. 32 | | ======================= | | SOURCE: MMWR 44(35);653 DATE: Sep 08, 1995 | | In the article, "Human Granulocytic Ehrlichiosis -- New York, | | 1995," references 4,5, and 3 at the end of the second and third | | sentences of the Editorial Note on page 594 should be renumbered | | (3,4) and (5), respectively; however, the numbers were attributed | | to the correct references in the list on the following page. | | The fourth and new fifth sentences of the first paragraph of | | the Editorial Note should read: "E. chaffeensis has most commonly | | been identified in the Lone Star tick (Amblyomma americanum) (6)." | | HGE patients reported having been bitten by "deer ticks" and "wood | | ticks" (possibly I. scapularis and Dermacentor variabilis, | | respectively) (2)." The new reference 6 is: Anderson BE, Sims KG, | | Olson JG, et al. Amblyomma americanum: a potential vector of human | | ehrlichiosis. Am J Trop Med Hyg 1993;49:239-44. | +------------------------------------------------------------------- ---+

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