Pathogenesis of anaplasmosis and ehrlichiosis

Epidemiological features

Infections caused by anaplasmas and ehrlichiae have a global geographical distribution and occur on all continents except Antarctica. For all pathogens in this group, except Neorickettsia sennetsu, a vector-borne transmission mechanism is characteristic. Bacteria enter the human body with the saliva of an infected ixodid tick during a bite.

An important feature of the pathogens' life cycle in the vector's organism is the absence of transovarial transmission — the infection is not passed on to the offspring of the infected tick. Human incidence has a pronounced seasonal character and directly correlates with tick activity in nature. All age groups of the population, from infants to the elderly, are susceptible to the infection. At the same time, true global incidence statistics have not been established due to the complexities of laboratory diagnostics and the lack of a mandatory case registration system. In European countries, the agent of granulocytic anaplasmosis is also frequently detected in dogs, roe deer, and horses.

Molecular and cellular pathogenicity factors

The mechanisms of the pathogenic action of anaplasmas and ehrlichiae are associated with several key factors. The immunopathological mechanism—cytokine aggression—plays a crucial role. Infected endothelial cells begin to produce excessive amounts of biologically active substances: tumor necrosis factor alpha (TNF-$\alpha$), interferon gamma (IFN-$\gamma$), and interleukin-10 (IL-10). This massive cytokine release leads to direct damage to target cells and triggers a cascade of pathological processes in tissues.

The life cycle of bacteria inside the cell is accompanied by the formation of special "spore-like" corpuscles. The exit of new pathogens from the affected cell occurs via "budding". This mechanism allows bacteria to infect neighboring healthy tissues without the immediate destruction of their host.

At the molecular level (using granulocytic ehrlichiosis as an example), aggression is provided by specific outer membrane proteins with a molecular mass of 44 and 153 kDa. These proteins function as adhesins, binding to lecithin-containing domains of cells, and are also capable of regulating gene expression within the infected host cell.

Pathogenesis features of Sennetsu fever

The pathogenesis of the disease caused by Neorickettsia sennetsu differs significantly in the localization of the port of entry and the dynamics of the process. Primary invasion of the pathogen occurs in the oropharynx, after which the infection spreads throughout the body via lymphatic and hematogenous routes.

Main links of the pathological process:

• Generalized lymphadenopathy — systemic enlargement of lymph nodes.
• Bone marrow involvement, leading to marked leukopenia (although transient neutrophilia may sometimes be recorded in the early stages of the disease).
• Damage to the capillary endothelial lining. Clinically, this manifests as the formation of an erythematous or petechial skin rash, which is recorded in approximately one-third of infected patients.

Pathogenesis of anaplasmosis and ehrlichiosis

Monocytic ehrlichiosis and granulocytic anaplasmosis are strictly associated with the vector-borne transmission route via the piercing-sucking apparatus of the tick. The initial stage of the disease starts at the moment the pathogen penetrates through the skin. An important differential diagnostic sign: no primary effect forms at the tick bite site.

Next, the dissemination stage begins: the pathogen enters the systemic circulation and is carried hematogenously to internal organs. The main target organs are structures rich in macrophages—the spleen, liver, lymph nodes, and bone marrow.

Focal necroses appear in the affected tissues, and perivascular lymphohistiocytic infiltrates are formed. Severe damage to hematopoiesis is of particular importance: megakaryocytopoiesis and hemophagocytosis actively proceed in the hematopoietic organs, ultimately leading to myeloid hypoplasia.

Clinical and morphological consequences

The described pathological changes in blood vessels and organs inevitably lead to the formation of a severe symptom complex. The clinical picture of the infections usually has a sudden onset and is always accompanied by fever.

Key consequences of systemic damage:

• Hemodynamic disorders: patients exhibit progressive arterial hypotension.
• Hemorrhagic syndrome: vascular and blood component damage may manifest as gastrointestinal and pulmonary bleeding.
• Laboratory shifts: blood tests reveal leukopenia and thrombocytopenia. Due to hepatocyte cytolysis, a biochemical blood test shows an increase in liver transaminases.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Molecular functions of anaplasma outer membrane proteins (44 and 153 kDa)
• Mechanisms of hemophagocytosis in hematopoietic organs during myeloid hypoplasia
• The role of the cytokine cascade (TNF-α, IFN-γ, IL-10) in endothelial damage
• Morphological characteristics of perivascular lymphohistiocytic infiltrates

Other topics in the section "Anaplasmas, Ehrlichiae"

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