PATHOGENS

Ehrlichia spp. are gram-negative, small, obligatory intracellular bacteria that primarily invade leukocytes of animals and humans. They appear as minute, round bacteria (cocci), about 1 µm in diameter. In the leukocytes, ehrlichiae divide by binary fission, developing from elementary to initial bodies to finally form vacuole-bound colonies known as morulae (plural for morula, 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.

The pathogens are transmitted by vectors in which they replicate. In the Ehrlichia canis genogroup, these vectors are generally ticks.

Transmission electron microscopical image of morulae in a bone marrow leukocyte of a human ehrlichiosis patient. Arrows indicate individual ehrlichiae.

Classification

In the order Rickettsiales, the family Anaplasmataceae contains four genera of medical importance: Ehrlichia, Anaplasma, Neorickettsia and Aegyptianella.

The genus Ehrlichia nowadays comprises the species Ehrlichia canis, Ehrlichia chaffeensis, Ehrlichia ewingii, Ehrlichia muris and Ehrlichia (Cowdria) ruminantium. These species are united into the ‘E. canis genogroup’. Members of the Ehrlichia genus are implicated as pathogens of dogs, cats, ruminants, horses and humans.

 

Ehrlichial agents known to infect dogs and cats 

Species	Common name of disease(s)	Common natural host(s)	Cells most commonly infected	Primary vector(s)	Distribution	Clinical Disease (*Human Disease)a
Ehrlichia canis	Canine monocytic ehrlichiosis (CME)	Dogs, wolves, jackals (members of the family Canidae) (humans)	Primarily mononuclear cells (monocytes, macrophages, lymphocytes)	Rhipicephalus sanguineus, (Dermacentor variabilis)	Worldwide, primarily tropical and temperate climates	Dogs: fever, lethargy, thrombocytopenia, anorexia, myalgia, lymphadenopathy, bleeding diatheses Cats: fever, lethargy, anorexia *Identified in Venezuela
Ehrlichia chaffeensis	Human monocytic ehrlichiosis (HME)	Humans, dogs, deer (horses, rodents)	Monocytes, macrophages, lymphocytes	Amblyomma americanum, Dermacentor variabilis	USA, Europe, Africa, South and Central America	Dogs: mild/subclinical unless present in co-infection Cats: not reported *Human monocytic ehrlichiosis
Ehrlichia ewingii	Canine granulocytic ehrlichiosis (CGE) (mild form), human granulocytic ehrlichiosis (HGE)	Dogs (humans)	Primarily neutrophils and eosinophils	Amblyomma americanum, Otobius megnini	USA	Dogs: fever, polyarthritis, thrombocytopenia, neurologic disease Cats: not reported *Granulocytic ehrlichiosis, uncommon
Ehrlichia (Cowdria) ruminantium	Heartwater disease	Ruminants	Endothelial cells, moncytes, macrophages, neutrophils	Amblyomma spp.	Africa, Caribbean	Dogs: subclinical/rare Cats: not reported

^afrom Allison & Little (2013)

 

Ehrlichia canis is responsible for the widespread canine monocytic ehrlichiosis (CME) in tropical and temperate areas of the world. The geographical distribution of E. canis has expanded with the distribution of its tick vector, the Brown Dog tick Rhipicephalus sanguineus.

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. It is the agent of human monocytic ehrlichiosis (HME). Ehrlichia chaffeensis could be detected by PCR in naturally infected dogs that were sick or healthy at the time of testing.

Ehrlichia sp. morulae in the cytoplasm of a monocyte

Ehrlichia ewingii primarily infects neutrophils and occasionally eosinophils and produces a disease clinically similar to HME and HGA (human granulozytic anaplasmosis). Most patients with ehrlichiosis caused by E. ewingii also had other medical conditions causing immunosuppression. In the USA, this pathogen generally causes a milder form of disease in dogs referred to as canine granulocytic ehrlichiosis (CGE). Infection with E. ewingii frequently induces polyarthritis in dogs and occasionally causes neurological disease in dogs and human patients.

Ehrlichia sp. morula in the cytoplasm of a neutrophil

Ehrlichia (Cowdria) ruminantium is the agent of heartwater disease in ruminants in Africa and the Caribbean. Based upon PCR amplification and DNA sequencing, E. ruminantium has been found in blood samples from dogs and HIV-infected humans in South Africa.

Human pathogenic Ehrlichiae

Recently several Ehrlichia spp. have been recognized as emerging human pathogens. Human monocytic ehrlichiosis (HME) is caused by E. chaffeensis, and E. ewingii, which was previously known as a canine pathogen, has also been recognized as human pathogen. Additionally an asymptomatic infection of a human patient in Venezuela was associated in molecular biological examinations with E. canis. Furthermore an E. ruminantium-like organism was recently found in humans and deer in the southeastern USA. Generally, with the exception of E. muris, all may be human pathogens.

Further pathogenic Anaplasmataceae

Another genus of medical importance of the family Anaplasmataceae is Neorickettsia. Besides a relevant human pathogen species (Neorickettsia sennetsu), the species Neorickettsia risticii and Neorickettsia helminthoeca have been reported to cause clinical signs in dogs, and antibodies have been detected in the sera of dogs and cats among others. In cats the former only caused clinical signs experimentally, while in the latter no feline disease is reported.