Main stages of infection development (early phases)
The development of brucellosis proceeds in strict stages. Natural human susceptibility to the infection is very high, and post-infection immunity is short-lived—only 6–9 months. There are five main phases of pathogenesis.
1. Lymphogenic phase The pathogen enters the body through damaged skin or mucous membranes. Due to the phenomenon of incomplete phagocytosis, the bacteria do not perish but survive inside macrophages and neutrophils. These cells carry Brucella to regional lymph nodes, where bacterial multiplication and accumulation take place. Clinically, this stage corresponds to the incubation period. The process of sensitization gradually begins in the body.
2. Hematogenous phase Characterized by a breakthrough of the pathogen and its toxins into the blood (bacteremia and toxinemia). Via the bloodstream, Brucella disseminate to the organs of the macrophage system: liver, spleen, kidneys, lungs, and bone marrow. Endotoxin (lipopolysaccharide complex) and inflammatory mediators cause severe toxic-allergic reactions and dysregulation of the autonomic nervous system. This stage manifests as acute brucellosis.
3. Phase of multi-focal localizations Bacteria settle and become fixed in the organs of the mononuclear phagocyte system. Macrophages accumulate around cells harboring intracellularly parasitic Brucella, diffuse productive inflammation develops, and specific brucellar granulomas are formed. Subsequently, bacteria periodically escape from these granulomas, provoking new waves of lympho-hematogenous dissemination. Clinically, this corresponds to the period of subacute brucellosis.
Late phases of pathogenesis and outcomes
4. Phase of extrafocal dissemination and reactive-allergic changes This stage occurs during the period of chronic brucellosis. By this point, the formation of humoral and non-sterile cellular immunity is complete (phagocytosis becomes completed). Episodes of dissemination, bacteremia, and toxinemia subside.
Morphologically, older granulomas undergo regression: they resolve, sometimes suppurate, or become fibrotic. However, against the background of severe immunopathological reactions, new foci of reactive granulomatous inflammation arise. This leads to severe functional disorders in various organ systems.
5. Phase of residual metamorphosis This is the stage of residual effects and outcomes. Its main and fundamental criterion is the complete absence of the pathogen in the body. Nevertheless, due to the prolonged preceding inflammation, the patient retains irreversible organic (scarring) or persistent functional tissue changes.
Pathomorphological changes by period
The degree and nature of tissue damage directly depend on the stage of the disease, as reflected in G.P. Rudnev's classification:
- Acute brucellosis (up to 1–1.5 months): alteration and serous interstitial inflammation predominate in the organs of the macrophage system, along with infectious-allergic vasculitis.
- Subacute brucellosis (from 1.5 to 4 months): productive inflammation comes to the forefront, characterized by the formation of brucellar granulomas (in lymph nodes, liver, spleen, synovial membranes). Dystrophy of internal organs joins in.
- Chronic brucellosis (over 4 months): granulomatous reactions persist, but fibrotic and sclerotic changes begin to actively develop. Lesions may involve the locomotor apparatus, nervous, urogenital, and cardiovascular systems.
- Residual brucellosis: the inflammatory process subsides, and morphologically only established sclerotic and fibrotic deformations are detected.
Briefly: answers to topical questions
Which Brucella species cause disease in humans?
Four species of Brucella, differing in their degree of pathogenicity, can cause disease in humans.
- Brucella melitensis (Br. melitensis) — the most dangerous and virulent for humans; goats and sheep serve as the reservoir.
- Brucella abortus (Br. abortus) — less pathogenic for humans; widespread in cattle.
- Brucella suis (Br. suis) — less pathogenic for humans; found in pigs, hares, and reindeer.
- Brucella canis (Br. canis) — causes disease in humans only in rare cases; affects dogs.
The species Br. ovis and Br. neotomae are non-pathogenic for humans.
Through which virulence factors are Brucella able to survive inside macrophages?
The survival of Brucella inside cells is due to virulence factors that provide resistance to phagocytosis and cellular invasion.
- Urease enzyme — provides defense against phagocytosis; its activity is especially important at the initial stage of the infectious process.
- Type 4 secretion system — injects effector molecules into the cell, promoting intracellular penetration.
- Outer membrane proteins and LPS — structural elements that also facilitate the invasion process.
The most important virulence factor overall is the pronounced resistance of the pathogen to phagocytosis.
To memorize the five phases of brucellosis pathogenesis, use the acronym L-H-P-E-R: Lymphogenic, Hematogenous, Polyfocal, Extrafocal, Residual.
Class and exam questions
Why do patients with acute brucellosis often feel satisfactory despite high fever?
This is a characteristic specific feature of brucellosis intoxication. Despite bacteremia, high fever, chills, and sweats, patients' overall well-being may remain relatively good.
How does residual brucellosis differ from chronic brucellosis?
The main criterion of the residual phase is the complete absence of the pathogen in the body. The entire clinical picture is associated not with active infection, but with the irreversible consequences of the previous inflammation (fibrosis, sclerosis).
What is the essence of the incomplete phagocytosis phenomenon in brucellosis?
Macrophages and neutrophils engulf Brucella but cannot destroy them. As a result, the bacteria survive, multiply inside immune system cells, and are carried by them throughout the body.
What else to study on this topic
- Clinical picture and criteria for the severity of acute brucellosis
- Forms of chronic brucellosis (osteoarticular, nervous, urogenital, visceral)
- Features of the asymptomatic course and the Burnet skin test
- Epidemiology of brucellosis: transmission factors and seasonality
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