DEPARTMENT OF PATHOLOGY
The Johns Hopkins Medical Institutions

Vol. 15 No.11

MICROBIOLOGY NEWSLETTER

Monday, March 11, 1996

A. Maryland Department of Health and Mental Hygiene, Epidemiology and Disease Control Program, Carmela Groves:

No report since last issue.

B. The Johns Hopkins Hospital (Information provided by Jean M. Henneberry, M.D., Pathology Resident)

Clinical History: The patient is a 42 y.o. previously healthy female residing in Watonga, OK. She had spent the later part of the month of May at a National Guard camp near Muskogee, OK, where she reportedly sustained multiple tick bites. During the first few days of her camp stay, she recalls having removed three ticks off her extremities. Later on that week, while on a weekend excursion to Texas, she removed an additional eight ticks with the assistance of her mother. Unfortunately, the ticks were discarded. However, she recalls that they were small and engorged and lacked any specific surface markings. She returned to the camp and soon became acutely ill with fevers and chills. She returned home and went to a local hospital in Watonga, where she was treated with IV fluids and discharged home on Augmentin. Over the next 24 hours her fevers persisted and she became extremely weak and lethargic. She returned to her local hospital, where she was admitted and placed on IV Vibramycin. Despite antibiotic therapy, her symptoms rapidly progressed. Fearful of Lyme disease or some other tick-borne ailment, her husband placed her in the car and drove all night to St. Francis Medical Center in Missouri. Upon admission to St. Francis, she had a temperature of 103°F and a WBC of 2,900 with 58% segs, 32% lymphs and 8% monos. Her WBC count from Watonga hospital was 3,800 and reached a nadir of 1,800. Other laboratory studies include the following: Hct 39%, CK 150, LDH 250 and AST 137.

She had a fairly severe headache and a stiff neck with some demonstrable nuchal rigidity. There were no rashes, however, small erythematous areas where the ticks had been removed were appreciated. A lumbar puncture was performed and the CSF findings were unremarkable. Blood and CSF samples were sent to Dr. J. Stephen Dumler and were positive for Ehrlichia chaffeensis by PCR methods. Serological studies demonstrated greater than a four-fold increase in E. chaffeensis titer.

Course: The patient received IV doxycycline for 5 days and showed dramatic resolution of symptoms. She was discharged home on a 2 week course of oral doxycycline.

Background: Ehrlichiae are obligate intracellular pleomorphic gram negative bacteria belonging to the family Rickettsiaceae. The organisms have a tropism for mononuclear or polymorphonuclear leukocytes and exist within membrane-lined cytoplasmic vacuoles (morulae) within the infected host cells. Although classically associated with zoonotic infections in canidae and cattle, several species have been identified in humans.

E. sennetsu, the causative agent of sennetsu fever or sennetsu ehrlichiosis was first isolated in humans in 1953. However, it was mistakenly identified as the etiologic agent of a disease described in southeast Japan since the late 19th century as infectious mononucleosis. The disease is self-limiting and serious complications or fatalities have not been reported.

In 1986, the first case of human ehrlichiosis was described in the United States. The causative agent, identified as a new ehrlichia species was named E. chaffeensis, after Fort Chaffee in Arkansas, where the patient from whom the first was residing. Sequence analysis and PCR studies of the 16S rRNA gene indicated that although unique, E. chaffeensis was closely related to E. canis, a species which causes disease in domestic and wild canidae. The disease is transmitted by ticks and causes a potentially life-threatening acute febrile illness. The characteristic features include fever, malaise, headache, myalgias, leukopenia, thrombocytopenia and elevated liver transaminases. Some cases may be asymptomatic resulting in seroconversion only. In contrast to Lyme disease and Rocky Mountain Spotted Fever, rash is variably present and non-specific.

Epidemiology: Most cases of Human Ehrlichiosis have been identified in the South-central and Mid-Atlantic regions of the United States. The peak infection period is from May through July and the incidence tends to be higher in men and in residents of rural areas.

Pathogenesis: The pathogenesis is poorly understood. Leukocytes and platelets appear to be the target cells of infection by different Ehrlichia species, however, the organisms have been identified in a variety of organs. The organisms replicate by binary fission within the host cells to form elementary bodies and morulae. The cell ruptures and the released ehrlichiae are phagocytosed, beginning a new infectious cycle.

Human Granulocytic Ehrlichiosis (HGE): Recently a new ( yet to be named ) species of Ehrlichia has been identified as the etiologic agent of HGE. The clinical manifestations are similar to those seen with E. chaffeensis infection and include fever, chills, headache, myalgias, thrombocytopenia and elevated liver transaminases. Rash is rare.

Identification and Diagnosis: Ehrlichiosis may be difficult to diagnose, as the signs and symptoms may be non-specific and lack of a tick bite or exposure may not raise the appropriate clinical suspicion. The diagnosis is currently based on serology (by indirect fluorescent antibody test) with the demonstration of a four-fold change in antibody titers, with at least one titer of 1:128 or greater. Isolation of Ehrlichia species has been accomplished by inoculating the leukocyte fraction of peripheral blood from infected patients into cell culture. A canine macrophage cell line, DH82, has been used for the isolation of E. chaffeensis. Recently a human promyelocytic leukemia cell line, HL60, has been used for the cultivation of the new Ehrlichia species.

PCR techniques have been used for the detection of Ehrlichia in blood and CSF. Evaluation of the peripheral blood smear for typical Ehrlichia moralae (inclusions) is extremely insensitive.

Treatment: Tetracyclines and their derivatives are the antibiotics of

choice for all species. Treatment must be initiated empirically in patients

with suspected ehrlichiosis due to its rapid onset and potentially fatal outcome.

Chloramphenicol may be used effective as an alternative drug in pregnant women and young children.

The role of chloramphenicol is controversial.

References:

Anderson, BE et al. Ehrlichlia chaffeensis, a New Species Associated with Human Ehrlichiosis. J Clin Microbiol, 1991;29:2838-2842.

Dawson, JE et al. Isolation and Characterization of an Ehrlichia sp. from a Patient Diagnosed with Human Ehrlichiosis. J Clin Microbiol, 1991;29:2741-2745.

Fishbein, DB et al. Human Ehrlichiosis in the United States, 1985-1990. Ann Intern Med, 1994;120:736-743.

Goldman, DP et al. Human Ehrlichiosis: A Newly Recognized Tick-Borne Disease. Amer Fam Physician, 1992;46:199-208.

Goodman, JL et al. Direct Cultivation Of The Causative Agent Of Human Granulocytic Ehrlichiosis. N Engl J Med, 1996;334:209-215.

Dumler, JS et al. Human Ehrlichiosis: Hematopathology and Immunohistologic Detection of Ehrlichia chaffeensis. Hum Pathol, 1993;24:391-396.

Bakken, JS et al. Clinical and Laboratory Characteristics of human granulocytic ehrlichiosis. JAMA 1996; 275:199-205.



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