Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and Ehrlichia ewingii ehrlichiosis

Abstract

Anaplasma phagocytophilum, Ehrlichia chaffeensis and Ehrlichia ewingii are emerging tick-borne pathogens and are the causative agents of human granulocytic anaplasmosis, human monocytic ehrlichiosis and E. ewingii ehrlichiosis, respectively. Collectively, these are referred to as human ehrlichioses. These obligate intracellular bacterial pathogens of the family Anaplasmataceae are transmitted by Ixodes spp. or Amblyomma americanum ticks and infect peripherally circulating leukocytes to cause infections that range in clinical spectra from asymptomatic seroconversion to mild, severe or, in rare instances, fatal disease. This review describes: the ecology of each pathogen; the epidemiology, clinical signs and symptoms of the human diseases that each causes; the choice methods for diagnosing and treating human ehrlichioses; recommendations for patient management; and is concluded with suggestions for potential future research.

Figure 1. Number of human monocytic ehrlichiosis, Ehrlichia ewingii ehrlichiosis, human granulocytic anaplasmosis and undetermined human ehrlichiosis cases per year (2003–2008)

Undetermined cases occur when all clinical criteria support Ehrlichia spp./Anaplasma phagocytophilum infection, but there is a lack of sufficient clarity to definitively classify the causative agent (e.g., morulae may have been identified in white cells in the absence of other supportive laboratory results). EEE: Ehrlichia ewingii ehrlichiosis; HGA: Human granulocytic anaplasmosis; HME: Human monocytic ehrlichiosis; UD: Undetermined. Data taken from [20].

Figure 2. Examples of Anaplasma phagocytophilum and Ehrlichia chaffeensis morulae in peripheral blood smears and tissue culture cells

(A & B) Anaplasma phagocytophilum and (C & D) Ehrlichia chaffeensis morulae within peripheral blood leukocytes of (A & C) infected human patients and (B & D) cultivated in vitro in (B) HL-60 human promyelocytic cells or (D) canine DH82 histiocytic lymphoma cells. Representative morulae are indicated by arrows. (A & C) Wright stain, original magnification ×1000, (B & D) LeukoStat stain, original magnification ×1000. (E & F) Electron micrographs of A. phagocytophilum-infected HL-60 cells. (E) A. phagocytophilum exhibits a biphasic developmental cycle and transitions between two distinct morphological forms, the dense cored cell (DC) and reticulate cell (RC); original magnification ×8200. Arrows and arrowheads delineate representative morulae containing DC or RC, respectively. (F) An arrow points to an A. phagocytophilum DC bound to the surface of and inducing its own phagocytic uptake by a HL-60 cell; original magnification ×26,500. Electron micrographs are provided by Matthew J Troese of Virginia Commonwealth University (VA, USA).