A 56-year-old man with a history of Wegener granulomatosis presented
with 6 days of sinus congestion, fever, malaise, myalgias, episcleritis, and
a morbilliform rash. An exacerbation of Wegener granulomatosis was the principal
concern because of the frequency of flares in that disease. The patient developed
acute renal failure, thrombocytopenia, transaminitis, and, finally, severe
myocarditis that led to congestive heart failure. Additional history-taking
and the evolution of his clinical features led to empirical treatment with
doxycycline for human monocytic ehrlichiosis (HME). The diagnosis of HME was
confirmed by both a polymerase chain reaction assay for Ehrlichia chaffeensis and by the demonstration of morulae within peripheral
blood mononuclear cells. The patient improved promptly following institution
of doxycycline, and his cardiac function returned to normal over a period
of 4 months.
A, Peripheral blood smear obtained on hospital day 1 showing a monocyte
with 2 vacuoles (morulae) that contain E chaffeensis clusters
(arrowheads) (Wright stain; original magnification ×240). B, E chaffeensis infects mononuclear phagocytes in blood and in tissues.
In the absence of an immune response, the bacterium is internalized via endocytosis.
After entry, dense core cells differentiate into reticulate cells that are
suspected to be the metabolically active and replicative stage. By poorly
understood mechanisms, E chaffeensis directs early
endosomes containing the bacteria into a receptor-salvage pathway that precludes
lysosomal fusion. Likewise, infection alters signal transduction pathways
and is associated with significant changes in host cell gene transcription.
These events lead to global down-regulation of innate immune response pathways
and receptor expression, intracellular vesicular trafficking, and activation
of antiapoptotic survival mechanisms. The net effect is a more hospitable
environment for intracellular replication. Replicated bacteria are released
by cell lysis or exocytosis to infect other mononuclear phagocytes nearby
or at disseminated sites. C, With emerging immune response, the bacteria are
opsonized by anti–E chaffeensis antibodies,
bound to Fc receptors, and phagocytosed. Ligation of antibody-bound E chaffeensis to Fc receptors triggers G-protein–coupled intracellular
signaling that results in destruction of the bacterium, degradation and presentation
of antigens for maturing adaptive immune response, and activation of innate
immune pathways. This process leads to the production of proinflammatory cytokines
and chemokines. Such responses are ultimately beneficial to the host by activation
of crucial CD4- and CD8-mediated immunity dominated by IFN-γ. However,
induction of proinflammatory mediators, including TNF-α, has the potential
to cause transient local tissue and organ injury or systemic manifestations.
Noninfected larvae obtain blood from a bacteremic vertebrate reservoir
host (eg, white-tailed deer), become infected, and maintain ehrlichiae when
the tick molts into the nymphal stage (trans-stadial [stage-to-stage] transmission).
Infected nymphs may transmit E chaffeensis to susceptible
reservoir hosts or incidentally to humans during acquisition of blood. Infected
adult ticks, having acquired ehrlichiae either by trans-stadial transmission
from the infected nymphal stage or during blood meal as noninfected nymphs
on infected deer, may also pass E chaffeensis to
other susceptible reservoirs or humans. Transovarial transmission (transmission
to the eggs and into larvae) has not been demonstrated, and eggs and unfed
larvae are presumably not infected. White-tailed deer (Odocoileus virginianus) are the predominant reservoir for E chaffeensis, although canids (eg, foxes, coyotes) are alternate reservoirs.
White-tailed deer can maintain a subclinical E chaffeensis bacteremia for months and are hosts of all 3 stages of Lone Star ticks,
its predominant vector. Photo provided by James Gathany/Centers for Disease
Control and Prevention.
Approximate geographic distribution of Amblyomma americanum in the United States.
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