Epidemiological Features
Infections caused by Anaplasma and Ehrlichia species have a global distribution and occur on all continents except Antarctica. For all pathogens in this group, except Neorickettsia sennetsu, transmission is vector-borne. Bacteria enter the human body via the saliva of an infected ixodid tick during a bite.
A crucial feature of the pathogen life cycle within the vector is the absence of transovarial transmission—the infection is not passed on to the offspring of the infected tick. Human incidence is strongly seasonal and correlates directly with tick activity in nature. All age groups, from infants to the elderly, are susceptible. However, true global incidence statistics remain unestablished due to diagnostic challenges and the lack of mandatory reporting systems in many regions. In European countries, the agent of granulocytic anaplasmosis is also frequently detected in dogs, roe deer, and horses.
Molecular and Cellular Pathogenicity Factors
The pathogenic mechanisms of Anaplasma and Ehrlichia involve several key factors. An immunopathological mechanism—cytokine aggression—plays a major 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 target cell injury and triggers a cascade of pathological tissue processes.
The intracellular life cycle of the bacteria involves the formation of distinctive spore-like corpuscles. The release of new pathogens from infected cells occurs via budding. This mechanism allows bacteria to infect adjacent healthy tissues without immediately destroying the host cell.
At the molecular level (using granulocytic ehrlichiosis as an example), virulence is mediated by specific outer membrane proteins with molecular weights of 44 and 153 kDa. These proteins function as adhesins by binding to lecithin-containing domains on host cells and can also regulate gene expression within the infected host cell.
Pathogenesis of Sennetsu Fever
The pathogenesis of the disease caused by Neorickettsia sennetsu differs significantly in the portal of entry and disease dynamics. Primary inoculation occurs in the oropharynx, after which the infection spreads via lymphatic and hematogenous routes.
Key links in the pathological process:
- Generalized lymphadenopathy — systemic enlargement of lymph nodes.
- Bone marrow involvement, leading to marked leukopenia (although transient neutrophilia may occasionally be noted in early stages).
- Damage to the capillary endothelium. Clinically, this manifests as an erythematous or petechial rash, observed in approximately one-third of infected patients.
Pathogenesis of Anaplasmosis and Ehrlichiosis
Monocytic ehrlichiosis and granulocytic anaplasmosis are strictly transmitted via the piercing-sucking mouthparts of ticks. The initial stage of the disease begins when the pathogen is introduced through the skin. An important differential diagnostic sign: no primary affect develops at the site of the tick bite.
Next comes the dissemination stage: the pathogen enters the systemic circulation and is carried hematogenously to internal organs. The primary target organs are structures rich in macrophages—the spleen, liver, lymph nodes, and bone marrow.
In affected tissues, focal necrosis develops along with perivascular lymphohistiocytic infiltrates. Severe involvement of hematopoiesis is particularly significant: megakaryocytopoiesis and hemophagocytosis occur actively in hematopoietic organs, ultimately leading to myeloid hypoplasia.
Clinical and Morphological Consequences
The described pathological changes in blood vessels and organs inevitably lead to a severe symptom complex. The clinical picture typically has a sudden onset and is always accompanied by fever.
- Hemodynamic disturbances: patients exhibit progressive arterial hypotension.
- Hemorrhagic syndrome: vascular and hematologic damage may manifest as gastrointestinal and pulmonary hemorrhage.
- Laboratory shifts: blood tests reveal leukopenia and thrombocytopenia. Due to hepatocyte cytolysis, biochemical analysis shows elevated hepatic transaminases.