Human Granulocytic Ehrlichiosis in the Upper Midwest United States: A New Species Emerging?

Abstract

Objective. —To characterize the clinical presentation and course, laboratory findings, and treatment outcome of 12 patients with human granulocytic ehrlichiosis. Setting. —The 12 patients were male, ranged in age from 29 to 91 years, and contracted their illness in Wisconsin or Minnesota. Methods. —Cases were recognized by the presence of intracytoplasmic inclusions (morulae) in peripheral neutrophils of patients presenting with temperature of 38.5°C or higher, chills, severe headache, and myalgias. All patients had a complete blood cell count and blood chemistry profile. Blood smears were examined by light microscopy. All available paired serum samples were analyzed for presence of indirect fluorescent antibodies againstEhrlichia chaffeensis, Ehrlichia phagocytophila, andEhrlichia equi. Blood samples from 12 patients were subjected to polymerase chain reaction analysis using primers specific for theE phagocytophila/E equigroup, primers that include the agent identified in our patients, as well asE chaffeensis. Results. —Varying combinations of leukopenia, anemia, and thrombocytopenia were found in all but one patient. All 12 patients demonstrated morulae in the cytoplasm of neutrophils, but not in mononuclear white blood cells. Serum assays failed to detect antibodies againstE chaffeensis, but eight of 10 patients and seven of 10 patients tested had antibody titers of 1:80 or more forE phagocytophilaandE equi, respectively. Polymerase chain reaction products obtained with primers forE phagocytophila, E equi, and the granulocytotropicEhrlichiarevealed that seven patients were infected with the same agent. The results of serological assays or polymerase chain reaction strongly suggest that all 12 patients were infected byE phagocytophila, E equi, or a closely relatedEhrlichiaspecies. Two of the 12 patients died. The other 10 patients improved rapidly with oral doxycycline treatment. Conclusions. —We believe that all 12 patients have been infected with a granulocyticEhrlichiaspecies, reflecting a recently described new disease entity. The infective organism appears to be closely related toE phagocytophilaandE equi. The geographic domain of human granulocytic ehrlichiosis is currently unknown. This novel granulocyticEhrlichiaspecies is capable of causing fatal infections in humans. Early detection and treatment with tetracycline drugs appear to offer the best chance for complete recovery. (JAMA. 1994;272:212-218)