print

Ehrlichiosis

back

Pathogens

Ehrlichia

Ehrlichia spp. are gram-negative, small, obligatory intracellular bacteria. They are transmitted by vectors in which they replicate (tick or trematode) and infect blood cells of animals or humans. In the E. canis genogroup, these are generally ticks. Within the mammal host, the pathogens show a tropism to white blood cells.

Classification

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

Genetic analysis of 16S rRNA genes, heat shock and surface proteins have resulted in a reclassification of the genus Ehrlichia. The genus Ehrlichia nowadays comprises the species E. canis, E. chaffeensis, E. ewingii, E. muris and E. (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.

Species

Common name of disease(s)

Common natural host(s)

Cells most commonly infected

Primary vector(s)

Distribution

Ehrlichia canis

Canine monocytic ehrlichiosis (CME)

Dogs, wolves, jackals (members of the family Canidae) (humans)

Primarily mononuclear cells

Rhipicephalus sanguineus, (Dermacentor variabilis)

Worldwide, primarily tropical and temperate climates

E. chaffeensis

Human monocytic ehrlichiosis (HME)

Humans, dogs, deer (horses, rodents)

Monocytes, macrophages

Amblyomma americanum, Dermacentor variabilis

USA, Europe, Africa, South and Central America

E. ewingii

Canine granulocytic ehrlichiosis (CGE) (mild form), human granulocytic ehrlichiosis (HGE)

Dogs (humans)

Primarily neutrophils and eosinophils

Amblyomma americanum, Otobius megnini

USA

E. muris

Not currently associated with disease

Rodents, humans

Mononuclear cells

Haemaphy- salis spp.

Japan

E. ondiri

Ondiri disease, bovine petechial fever

Cattle, sheep

Granulocytes

Unknown

Africa

E. (Cowdria) ruminantium

Heartwater disease

Rumi nants

Endothelial cells

Amblyomma spp.

Africa, Caribbean

E. ruminantia like organism

Humans, deer, goats

Amblyomma americanum (implicated)

Southeastern USA


Figure 1: Neighbour-joining phylogenetic tree of 16S rRNA gene sequences of species formerly known as Ehrlichia. GenBank database accession numbers are indicated in parenthesis. The scale bar indicates the number of substitutions/site. (With permission of E.B. Breitschwerdt)

Different species cause different forms of ehrlichiosis

Ehrlichia was 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.

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. More recently, E. chaffeensis and E. ewingii have been identified by PCR in naturally infected dogs, with or without clinical signs consistent with ehrlichiosis.

Both pathogens meanwhile have also been reported from Africa and Asia (Korea) apart from the former areas of distribution (America and Europe).

E. 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 chaffeens could be detected by PCR in naturally infected dogs that were sick or healthy at the time of testing.

E. 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 have also had other medical conditions causing immunosuppression (e.g., HIV infection, splenectomy, transplantation, immunosuppressive drugs). In the USA, this pathogen generally causes a milder form of disease 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.

E. (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.

A novel Ehrlichia transmitted by Amblyomma americanum was recently discovered in Panola Mountain State Park, Georgia, USA. The "Panola Mountain Ehrlichia" (PME) is closely related to E. ruminantium and caused transient febrile illness, followed by chronic latent infection, in a goat. The agent was also associated with a case of human illness and white-tailed deer are representing a probable vertebrate reservoir the United States.

Disease manifestations caused by the various Ehrlichia species that infect dogs and human beings can be indistinguishable, and there may be strain variation in pathogenicity. Severe life-threatening chronic ehrlichiosis can develop in association with persistent E. canis infection, with resultant irreversible bone marrow destruction. Co-infection, breed-specific immune response and strain variation could all play a role in the disease manifestations and pathology found in individual dogs following chronic infection.

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

Detailed information on members of the genus Anaplasma spp. can be found in the section anaplasmosis. In the following the other two genera of medical importance of the family Anaplasmataceae are shortly listed: Within the genus Neorickettsia the species Neorickettsia sennetsu is relevant as human pathogen causing a mononucleosis-like infection discovered in Japan in the 1950’s and recently found in Malaysia. The species N. risticii and N. helminthoeca are of veterinary relevance. The former causes the ‘Potomac horse fever’ and antibodies have also been detected in sera of dogs, cats, coyotes, pigs and goats. It is reported to cause an atypical syndrome of monocytic ehrlichiosis in dogs in the USA. The latter is the agent of ‘Salmon poisoning disease’, occasionally occurring in dogs, foxes and coyotes in the USA after ingestion of raw salmons which contained N. helminthoeca-infected trematodes. Finally the genus Aegyptianella contains blood pathogens of birds, amphibians and reptiles.

E. muris, detected in mice and in humans (antibody detection in sera of Japanese), is not thus far associated with clinical symptoms in human patients or clinical signs in dogs.

The Ehrlichia organism

Ehrlichiae are small, gram-negative, obligatory intracellular bacteria that primarily invade leukocytes, the same cells which fight disease by destroying microorganisms that enter the body. Ehrlichiae typically 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, 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 2: Electron photo micrograph of morulae in a bone marrow leukocyte in a human patient with ehrlichiosis. Arrows indicate individual ehrlichiae.

   

Ehrlichia chaffeensis primarily infects mononuclear leukocytes (predominantly monocytes and macrophages).
(Morulae in cytoplasm of monocyte.)

   

Ehrlichia ewingii primarily infects neutrophils and occasionally eosinophils and was described as the agent of a mild form of canine granulocytic ehrlichiosis (CGE).
(Morula in cytoplasm of neutrophil.)

   

Further information

  • Breitschwerdt EB, Hegarty BC, Hancock SI: Sequential evaluation of dogs naturally infected with Ehrlichia canis, Ehrlichia chaffeensis, Ehrlichia equi, Ehrlichia ewingii, or Bartonella vinsonii. J Clin Microbiol. 1998, 36, 2645-51
  • Neer TM, Breitschwerdt EB, Greene RT, et al.: Consensus statement on ehrlichial disease of small animals. J Vet Intern Med. 2002, 16, 309-15
  • Shaw SE, Day MJ, Birtles RJ, et al.: Tick-borne infectious diseases of dogs. Trends Parasitol. 2001, 17, 74-80
  • http://www.cdc.gov/ehrlichiosis/

Occurrence Maps

Each country has its specific occurrence of CVBDs depending on climate and endemic vectors. See the maps

Clinical Sessions

The following authentic case reports provide insights into selected CVBD cases

View all

Interesting Links

CVBD and parasito­logical relevant websites. More...

CVBD Digest Articles

Findings from the CVBD symposia. More...