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Morphology and Biology of Anaplasma and Ehrlichia

Anaplasma, Ehrlichia

For medical students2 min readUpdated 2026-10-10

Anaplasma and Ehrlichia are small, pleomorphic, obligate intracellular bacteria. Their key biological feature is the ability to replicate within cytoplasmic vacuoles of phagocytic cells, forming characteristic microcolonies known as morulae.

MorphologyCoccoid or ovoid bacteria, staining purple with Romanowsky-type stains.
MorulaeAggregations of the pathogen inside vacuoles resembling mulberries (ranging from 3 to 50 bacteria).
CultivationVery slow growth in cell cultures, taking from 20 to 40 days.
Cell TropismThe bacteria selectively infect monocytes, macrophages, and other blood cells.

Morphological and Staining Properties

The pathogens are characterized by small dimensions and marked pleomorphism—microscopic preparations reveal both coccoid and ovoid forms. Electron microscopy confirms that the ultrastructure of these microorganisms shares significant similarities with rickettsiae.

However, unlike typical rickettsiae, Ehrlichia and Anaplasma exhibit a distinct cellular tropism. When blood smears are stained with Romanowsky stain, these intracellular microorganisms acquire an intense dark blue or purple hue. Bacterial cell replication occurs via classical binary fission.

Intracellular Parasitism and Morula Formation

The lifecycle of these pathogens occurs strictly within cytoplasmic vacuoles (phagosomes or endosomes) of infected cells. Monocytes, macrophages, and circulating blood cells are primarily affected.

A hallmark of Anaplasma and Ehrlichia biology is the formation of dense, compact bacterial clusters inside phagosomes that visually resemble a mulberry fruit. These specific structures are termed morulae.

Quantitative characteristics of the infectious process vary:

This feature is critical for laboratory diagnosis. In blood smears, the proportion of infected leukocytes is typically very low, ranging from 0.3% to 6%, requiring meticulous examination during screening.

Cultivation and Antigenic Structure

Isolation of Anaplasma and Ehrlichia from patients is challenging due to their fastidious culture requirements. These bacteria grow exclusively in cell cultures, such as macrophage-like lines (e.g., canine macrophages) and standard continuous cell lines like Vero and HeLa. Biomass accumulation is extremely slow and prolonged, with cultivation taking anywhere from 20 to 40 days.

The antigenic structure of members of the family Anaplasmataceae features important characteristics. They share no specific cross-reacting antigens with the typhus group or spotted fever group rickettsiae. However, significant antigenic cross-reactivity is observed within the family among related species pathogenic to animals.

Laboratory animal models exist for studying certain species. For instance, Neorickettsia sennetsu can be studied using white mice, in which the pathogen causes a severe generalized infection characterized by massive bacterial accumulation in the spleen and peritoneal macrophages.

Classification of Major Species

Modern classification is based on the type of host cells infected and the specific species of pathogen.

1. Monocytic Ehrlichiosis

2. Granulocytic Anaplasmosis

3. Sennetsu Neorickettsiosis (Infectious Mononucleosis)

Mnemonic

To keep the major diseases straight: Monocytic ehrlichiosis targets monocytes (M-E), while Granulocytic anaplasmosis targets granulocytes (G-A). The intracellular bacterial clusters are called morulae because they resemble a mulberry (morus in Latin).

Frequently asked questions

What laboratory diagnostic methods are used to confirm ehrlichiosis and anaplasmosis?

Serological, molecular-genetic, and microscopic methods are used to confirm ehrlichiosis and anaplasmosis.

  • Serological assays — testing paired sera using IFA, indirect immunofluorescence assay (IFA/IIR), or ELISA with specific antigens.
  • Molecular-genetic assays — PCR detection of pathogen DNA (Anaplasma phagocytophilum, Ehrlichia muris, Ehrlichia chaffeensis) in blood.
  • Microscopy — Romanowsky-Giemsa staining of blood smears to search for pathogen clusters (morulae) inside the cytoplasm of monocytes or neutrophils.
Which antimicrobial agents are the drugs of choice for treating ehrlichiosis and anaplasmosis?

The drugs of choice for targeted therapy of ehrlichiosis and anaplasmosis are tetracycline-class antibiotics, primarily doxycycline. Chloramphenicol is used less frequently as an alternative agent.

What virulence and pathogenicity factors characterize Anaplasma and Ehrlichia?

Pathogenicity factors of Anaplasma and Ehrlichia include immunopathological mechanisms, specialized lifecycle traits, and specific molecular factors.

  • Cytokine storm — infected endothelial cells produce excess cytokines (TNF-$\alpha$, IFN-$\gamma$, IL-10), leading to target cell damage.
  • Lifecycle features — formation of "spore-like" elementary bodies and exiting the cell via budding, allowing infection of neighboring cells without immediate host cell lysis.
  • Molecular factors — outer membrane proteins (44 and 153 kDa) that act as adhesins and regulate host cell gene expression.
Why are Anaplasma and Ehrlichia so difficult to isolate from a patient?

This is due to their obligate intracellular parasitism: they grow exclusively in cell cultures, and their growth is extremely slow (20–40 days) with minimal pathogen yield.

What do the pathogens look like under light microscopy?

When stained with Romanowsky stain, they appear as coccoid or ovoid dark-blue or purple structures. They reside within cytoplasmic vacuoles as characteristic clusters called morulae.

How does sennetsu neorickettsiosis differ from other ehrlichioses in terms of transmission?

Unlike monocytic ehrlichiosis and granulocytic anaplasmosis, which are transmitted through ixodid tick bites, the vector for Neorickettsia sennetsu remains undetermined. Transmission occurs via the alimentary route through the consumption of raw fish.

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