Vol. 17, No. 46
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER
Monday, December 14 1998
A. Provided by Leslie Edwards Reger, Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene.
B. The Johns Hopkins Hospital. Information provided by Dr. Ann Smith, Department of Pathology.
Clinical Course and Laboratory Diagnosis: Because of leukopenia, thrombocytopenia, and fever unresponsive to antibiotic therapy, the patient was started on IV doxycycline for possible ehrlichiosis. One day post-operatively the patient’s white blood cell and platelet counts had partly corrected and her fever had decreased. The patient was extubated after four days and the doxycycline was discontinued. Ehrlichia chaffeensis and Borrelia burgdorferi titers from the acute phase of illness were 1:64 (borderline) and negative, respectively. However, a repeat E. chaffeensis titer one month later was 1:1,024. B. burgdorferi serology revealed a positive IgM, but no IgG antibodies by ELISA or western blot. Surgical Pathology confirmed the diagnosis of appendicitis with acute and xanthogranulomatous inflammation and the specimen was sent to Johns Hopkins for further studies. Immunohistochemical stains of the appendix revealed positive staining within monocytes with antibody to E. chaffeensis.
Epidemiology and Clinical Manifestations: Ehrlichia chaffeensis is the agent of human monocytic ehrlichiosis (HME). HME was first reported in 1987 in a 51-year-old man who became ill in April 1986, two weeks after tick bites in rural Arkansas. E. chaffeensis has been detected in two tick species, the lone star tick and the American dog tick. It is likely that deer, or other animals such as dogs or small rodents, serve as the reservoir host for E. chaffeensis and that the lone star ticks serve as the major vector. HME has been reported in 30 states of the United States, particularly the west-south-central and southeastern states. Most patients (83%) report exposure to ticks within three weeks of illness onset.
Clinically, patients present with a mild to severe multisystemic illness with about 40% of patient’s requiring hospitalization. Although HME presents as an acute illness or prolonged fever of undetermined origin in immunocompetent individuals, it is also an opportunistic pathogen in immunocompromised patients. The median incubation period is seven days. Signs and symptoms of ehrlichiosis include fever, chills, headache, myalgia, and malaise. Later in the course of the disease, patients develop nausea, anorexia, and abdominal pain. Physical examination in most often non-specific. Fewer than half of patients have a rash which can be maculopapular or petechial. Severe complications can occur and include respiratory and renal insufficiency, central nervous system abnormalities, GI hemorrhages, and death. Important laboratory findings include leukopenia, thrombocytopenia, and elevations in serum hepatic transaminases.
Pathogenesis, Treatment, and Prevention: E. chaffeensis is introduced into the dermis by the bite of an infected tick. The obligate intracellular bacteria spreads hematogenously throughout the body and establishes infection within phagosomes, most often in macrophages, in the liver, spleen, and lymph nodes. It can also be seen in bone marrow, lung, and kidney. Pathologic lesions in ehrlichiosis include focal necrosis, perivascular lymphohistiocytic infiltrates, hemophagocytosis, and interstitial pneumonitis. The pathogenic mechanisms of ehrlichial disease are poorly understood and the role of host immune and inflammatory responses has yet to be determined.
Tetracyline and doxycycline have been used successfully in the treatment of ehrlichiosis. Susceptibility tests have also shown rifampin to be ehrlichiacidal. Prevention of HME relies on avoidance of tick exposure, regular searches for ticks when exposure occurs, and prompt removal of ticks from the body.
Differential and Diagnosis: Differential diagnoses include viral syndromes, Rocky Mountain spotted fever, relapsing fever, Q fever, tularemia, Lyme disease, toxic shock syndrome, bacterial sepsis, and leukemia. Currently, laboratory diagnosis utilizes immunofluorescence assay (IFA) employing E. chaffeensis as the antigenic substrate. PCR using primers specific for sequences of the 16S rRNA gene and ehrlichial isolation are also performed. IFA serologic tests must show a fourfold rise in titer during the course of the disease, with a minimal peak titer of 1:80. Most patients show seroconversion 4 or more weeks after onset of illness and a decrease in titer to less than 80 by 17-31 weeks after onset. Immunohistologic demonstration of the ehrlichial morulae can be a highly specific and efficient means of diagnosis as demonstrated in the above case. However, this approach is relatively insensitive because a readily available patient sample which contains demonstrable organisms has not been identified.
Comment: The above case emphasizes the importance of considering ehrlichiosis in patients with a history of fever and possible tick exposure who present with rapidly progressive respiratory distress. In these cases, prompt implementation of therapy with broad-spectrum antibiotics may help to prevent the high mortality associated with ARDS.
Recently, a case report of perinatal transmission of the agent of human granulocytic ehrlichiosis (HGE) was published in The New England Journal of Medicine. In 1994, HGE was recognized as a distinctly separate infectious disease caused by E. phagocytophila which replicates within granulocytes circulating in peripheral blood. Although the authors of the neonatal HGE case suspected transplacental transmission as the route of transmission, they could not exclude other causes such as breast-feeding or intrapartum transmission. Regardless, the infected infant rapidly responded to therapy with doxycycline. Whether Ehrlichia infection impacted upon the patient’s pregnancy is unknown at this time.
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