Js. Bakken et al., HUMAN GRANULOCYTIC EHRLICHIOSIS IN THE UPPER MIDWEST UNITED-STATES - A NEW SPECIES EMERGING, JAMA, the journal of the American Medical Association, 272(3), 1994, pp. 212-218
Objective.-To characterize the clinical presentation and course, labor
atory findings, and treatment outcome of 12 patients with human granul
ocytic ehrlichiosis. Setting.-The 12 patients were male, ranged in age
from 29 to 91 years, and contracted their illness in Wisconsin or Min
nesota. Methods.-Cases were recognized by the presence of intracytopla
smic inclusions (morulae) in peripheral neutrophils of patients presen
ting with temperature of 38.5 degrees C or higher, chills, severe head
ache, and myalgias. All patients had a complete blood cell count and b
lood chemistry profile. Blood smears were examined by light microscopy
. All available paired serum samples were analyzed for presence of ind
irect fluorescent antibodies against Ehrlichia chaffeensis, Ehrlichia
phagocytophila, and Ehrlichia equi Blood samples from 12 patients were
subjected to polymerase chain reaction analysis using primers specifi
c for the E phagocytophilal E equi group, primers that include the age
nt identified in our patients, as well as E chaffeensis. Results.-Vary
ing combinations of leukopenia, anemia, and thrombocytopenia were foun
d in all but one patient. All 12 patients demonstrated morulae in the
cytoplasm of neutrophils, but not in mononuclear white blood cells. Se
rum assays failed to detect antibodies against E chaffeensis, but eigh
t of 10 patients and seven of 10 patients tested had antibody titers o
f 1:80 or more for E phagocytophila and E equi, respectively. Polymera
se chain reaction products obtained with primers for E phagocytophila,
E equi, and the granulocytotropic Ehrlichia revealed that seven patie
nts were infected with the same agent. The results of serological assa
ys or polymerase chain reaction strongly suggest that all 12 patients
were infected by E phagocytophila, E equi, or a closely related Ehrlic
hia species. Two of the 12 patients died. The other 10 patients improv
ed rapidly with oral doxycycline treatment. Conclusions.-We believe th
at all 12 patients have been infected with a granulocytic Ehrlichia sp
ecies, reflecting a recently described new disease entity. The infecti
ve organism appears to be closely related to E phagocytophila and E eq
ui. The geographic domain of human granulocytic ehrlichiosis is curren
tly unknown. This novel granulocytic Ehrlichia species is capable of c
ausing fatal infections in humans. Early detection and treatment with
tetracycline drugs appear to offer the best chance for complete recove
ry.