Epidemiologic Notes and Reports Human Ehrlichiosis -- United States

Human infection with Ehrlichia canis or another closely related rickettsia was described in the United States for the first time in 1986 (1). In April of that year, a 51-year-old man developed fever, malaise, myalgia, and headache approximately 12 days after being bitten by ticks while he was planting trees in rural Arkansas. He was hospitalized 5 days after becoming ill.

Upon admission to the hospital, the patient had an oral temperature of 39.7 degrees C (103.5 degrees F), leukopenia, thrombocytopenia, renal failure, and elevated liver enzymes, but no rash. A presumptive diagnosis of "spotless" Rocky Mountain spotted fever (RMSF) was made, and the patient was treated with chloramphenicol and, later, with doxycycline. Cytoplasmic inclusions were observed in peripheral lymphocytes, neutrophils, and monocytes on the seventh day of illness. His illness was complicated by disseminated candidiasis, but he was discharged after 12 weeks of hospitalization without residual problems. Serum samples obtained during the late acute and convalescent periods of illness were negative for antibodies against Rickettsia rickettsii and other agents, but there was a 16-fold decrease in antibody titers against E. canis (highest titer, 640) by indirect fluorescent antibody (IFA) test. In addition, examination of inclusions in leukocytes by electron microscopy revealed a structure that was compatible with rickettsia belonging to the genus Ehrlichia.

Since this initial case report, 45 additional cases of human ehrlichiosis have been identified by various investigators (2-5; CDC, unpublished data). All but eight of these cases were detected by testing serum samples from patients who had suspected RMSF but who were seronegative for R. rickettsii.

Seventy-four percent of patients were male, and the majority of patients were between 30 and 60 years of age (range = 2-68). Patients were exposed to infection in 11 states,* the majority of which are in the southeastern and south central areas of the country. These are the same areas from which the majority of serum specimens tested for E. canis were obtained. Onsets of illness occurred between March and October.

Eighty-three percent of patients had a history of tick exposure in the 4-week period before onset of illness; the majority were exposed to ticks 1 to 3 weeks before they became ill. Information on the species of ticks involved was not available.

Symptoms reported by patients were nonspecific (Table 1) and similar to those reported by patients with RMSF. However, approximately 20% of patients with ehrlichiosis reported a rash (frequently nonspecific), whereas 88% of those with RMSF reported a rash (6). One patient was asymptomatic. Over half of the patients had hematologic abnormalities such as leukopenia and thrombocytopenia (Table 1) and mildly abnormal liver function tests, especially aspartate aminotransferase and alanine aminotransferase (Table 1). Although 63% of patients were hospitalized, all recovered without residual problems. However, there has been a preliminary report of a human fatality possibly associated with E. canis infection. Reported by: Viral and Rickettsial Zoonoses Br, Div of Viral Diseases, Center for Infectious Diseases, CDC. Editorial Note:

Ehrlichia, members of the family Rickettsiaceae, are obligate, intracellular bacteria that parasitize mononuclear or polymorphonuclear leukocytes. The ability of Ehrlichia to infect and cause disease in animals is well documented (7). Canine ehrlichiosis, also known as tropical canine pancytopenia, is caused by E. canis and has an acute and chronic phase. After an incubation period of 10-14 days, dogs develop an acute febrile illness that may include depression, anorexia, lymphadenopathy, and thrombocytopenia (8). The chronic phase of the disease, which is often fatal, is characterized by pancytopenia and bone marrow hypoplasia. In the United States, serological evidence of E. canis infection has been reported among dogs in at least 34 states (9).

Preliminary data suggest that human ehrlichiosis, like canine ehrlichiosis, is tickborne. Although canine ehrlichiosis is transmitted by the brown dog tick, Rhipicephalus sanguineus, this tick is probably not the main vector or reservoir involved in human transmission since it rarely bites people (10). There is no evidence that human ehrlichiosis is transmitted directly from dogs to people (2,3).

Before 1986, only one Ehrlichia species, E. sennetsu, had been recognized as a human pathogen (11). Infection with E. sennetsu results in an acute febrile illness with lymphocytosis and postauricular and posterior cervical lymphadenopathy similar to mononucleosis. To date, this disease has been found only in Japan and Malaysia (7). Currently, the diagnosis of human ehrlichiosis is based on an IFA test that shows a fourfold or greater increase or decrease in antibody titer against E. canis with a minimum titer of 80. The test is a modification of the IFA test used for canine ehrlichiosis (12).

Tetracycline has been shown to be effective in both the acute and chronic phases of canine ehrlichiosis (13). Human ehrlichiosis appears to respond to tetracycline administered at the same dose and schedule used for RMSF. However, insufficient data exist to recommend chloramphenicol as an alternative antibiotic.

Physicians should consider the possibility of ehrlichiosis when patients have a febrile illness and a history of recent tick exposure. The diagnosis can be confirmed by testing acute- and convalescent-phase serum samples (taken 2-4 weeks apart) for E. canis antibody. Serologic testing for E. canis antibody is available at CDC. Only serum specimens submitted as pairs (i.e., acute- and convalescent-phase samples) will be accepted for testing. Specimens should be submitted to CDC through state health departments. References

1. Maeda K, Markowitz N, Hawley RC, Ristic M, Cox D, McDade JE. Human infection with Ehrlichia canis, a leukocytic rickettsia. N Engl J Med 1987;316:853-6.

2. Fishbein DB, Sawyer LA, Holland CJ, et al. Unexplained febrile illnesses after exposure to ticks: infection with an Ehrlichia? JAMA 1987;257:3100-4.

3. Fishbein DB, Taylor JP, Dawson J, et al. Human ehrlichiosis in the United States (Abstract no. 1277). In: Program and abstracts of the Twenty-Seventh Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 1987:319.

4. Rohrbach BW, Harkess JR, Ewing SA, Kudlac JF, McKee GL, Istre GR. Human ehrlichiosis, Oklahoma (Abstract no. 1278). In: Program and abstracts of the Twenty-Seventh Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 1987:319.

5. Taylor JP, Betz TG, Fishbein DB, Roberts MA, Dawson J, Ristic M. Serologic evidence of possible human infection with Ehrlichia in Texas. J Infect Dis (in press).

6. Helmick CG, Bernard KW, D'Angelo LJ. Rocky Mountain spotted fever: clinical, laboratory, and epidemiological features of 262 cases. J Infect Dis 1984;150:480-8.

7. Ristic M. Pertinent characteristics of leukocytic rickettsiae of humans and animals. In: Leive L, ed. Microbiology--1986. Washington, DC: American Society for Microbiology, 1986: 182-7.

8. Kuehn NF, Gaunt SD. Clinical and hematologic findings in canine ehrlichiosis. J Am Vet Med Assoc 1985;186:355-8.

9. Keefe TJ, Holland CJ, Salyer PE, Ristic M. Distribution of Ehrlichia canis among military working dogs in the world and selected civilian dogs in the United States. J Am Vet Med Assoc 1982;181:236-8.

10. Nelson VA. Human parasitism by the brown dog tick. J Econ Entomol 1969;62:710-2.

11. Tachibana N. Sennetsu fever: the disease, diagnosis, and treatment. In: Leive L, ed. Microbiology--1986. Washington, DC: American Society for Microbiology, 1986:205-8.

12. Ristic M, Huxsoll DL, Weisiger RM, et al. Serological diagnosis of tropical canine pancytopenia by indirect immunofluorescence. Infect Immun 1972;6:226-31.

13. Amyx HL, Huxsoll DL, Zeiler DC, Hildebrandt PK. Therapeutic and prophylactic value of tetracycline in dogs infected with the agent of tropical canine pancytopenia. J Am Vet Med Assoc 1971;159:1428-32.

*Alabama, Arkansas, Georgia, Missouri, New Jersey, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia. The state of residence was used for two persons with no history of tick exposure.

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