Human ehrlichiosis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Pathophysiology
Ehrlichiae are small, gram-negative bacteria that primarily invade leukocytes (white blood cells), the same cells which fight disease by destroying microorganisms that enter the body. Ehrlichiae typically appear as minute, round bacteria (cocci), ranging from 1 to 3 µm (micrometers) in diameter. In the leukocytes, ehrlichiae divide to form vacuole-bound colonies known as morulae (plural for morula, which is the Latin word for mulberry, referring to the mulberry-like clustering of the dividing organisms). The formation of morulae is a defining characteristic of this group of bacterial pathogens (Figure A).
Taxonomy
The genus Ehrlichia is currently classified as a member of the tribe Ehrlichieae, of the family Rickettsiaceae, in the order Rickettsiales. The genus includes seven recognized species: E. canis, E. chaffeensis, E. equi, E. phagocytophila, E. risticii, E. ewingii, and E. sennetsu. A number of other named ehrlichiae, such as E. platys, E. bovis, E. ovina, and E. ondiri also cause disease in animals (Table 1). The names of the latter organisms are enclosed in quotation marks because they have not been formally proposed and accepted according to the rules of the International Code of Nomenclature of Bacteria, Bacteriological Code.
The ehrlichiae were initially grouped according to the type of blood cell most commonly infected (granulocyte, lymphocyte, monocyte, platelet), and disease classes have been termed "granulocytic (or granulocytotropic) ehrlichiosis" or "monocytic (or monocytotropic) ehrlichiosis." However, this type of classification may be misleading because some of the Ehrlichia species have been found in cells other than their chief target cell type. In addition, more than one species may be responsible for the broad category of "monocytic" or "granulocytic" ehrlichiosis (e.g., compare the HGE agent and E. ewingii in the figures below).
- Figure B. Ehrlichia chaffeensis primarily infects mononuclear leukocytes (predominantly monocytes and macrophages), but may also be seen occasionally in the granulocytes of some patients with severe disease.
- Figure C. The pathogen that causes human granulocytic ehrlichiosis (HGE) primarily infects granulocytes (neutrophils and rarely eosinophils). The pathogen is often referred to as the agent of HGE or the HGE agent. This species is very similar, or likely identical, to E. phagocytophila and E. equi.
- Figure D. Ehrlichia ewingii primarily infects neutrophils and occasionally eosinophils and produces a disease clinically similar to HME and HGE. Most patients with this form of ehrlichiosis have also had other medical conditions causing immunosuppression (e.g., HIV infection, splenectomy, transplantation, immunosuppressive drugs).
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Figure B
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Figure C
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Figure D
Modern Classification
Using modern molecular biology techniques, we now know that Ehrlichia species form three distinct groups (see Figure 5 below). The species contained within these "genogroups" are also related to organisms not previously considered to be members of this genus. The classification of the genus Ehrlichia requires revision, and future studies may provide the additional data needed.
- Figure D. Genetic relationship of Ehrlichia species and other bacteria based on similarity of 16rRNA gene
