Human Monocytic Ehrlichiosis

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.