The disease brucellosis occurs worldwide, especially in Mediterranean and Persian Gulf countries, India, and parts of Mexico and Central and South America. The organisms are capable of survival for extended periods (e.g., soil, 10 weeks; aborted fetuses, 11 weeks; bovine stool, 17 weeks, milk and ice cream, 3 weeks); they can survive in fresh cheese for several months. Brucellosis is a zoonosis and is recognized as a cause of devastating economic loss among domestic livestock.
Each of the four Brucella spp. that are pathogenic for humans has a limited number of preferred animal hosts (Table 1). In the host, Brucella tend to localize in tissues rich in erythritol (e.g., placental tissue), a four carbon alcohol that enhances their growth. Humans become infected by four primary routes:
• Ingestion of infected unpasteurized animal milk products (most common means of transmission)
• Inhalation of infected aerosolized particles (laboratory-acquired infection is the most important source of transmission)
• Direct contact with infected animal parts through ruptures of skin and mucous membranes
• Accidental inoculation of mucous membranes by aerosolization
Table1. Brucella spp. and Their Respective Natural Animal Hosts
Rare cases of transmission by blood and bone marrow transplantation and by sexual intercourse, in addition to neonatal brucellosis, have been reported. Individuals considered at risk for contracting brucellosis include dairy farmers, livestock handlers, slaughterhouse employees, veterinarians, and laboratory personnel. The organ ism has a very low infectious dose (100 organisms or fewer). Mishandling and misidentification of the organism is often associated with laboratory transmission of the organism.
Brucella spp. are facultative, intracellular parasites that are able to exist in both intracellular and extracellular environments. Other bacteria classified as facultative intracellular infectious agents include Salmonella, Shigella, Yersinia, Listeria, and Francisella spp. After infecting a host, brucellae are ingested by neutrophils, within which they replicate, causing cell lysis. Neutrophils containing viable organisms circulate in the bloodstream and are subsequently phagocytized by reticuloendothelial cells in the spleen, liver, and bone marrow. If the infection goes untreated, granulomas develop in these organs, and the brucellae survive in monocytes and macrophages. Brucellae tend to show a tendency to invade and persist in the human host by inhibiting apoptosis (programmed cell death). Resolution of the infection depends on the host’s nutritional and immune status, the size of the inoculum and route of infection, and the Brucella species causing the infection; in general, B. melitensis and B. abortus are more virulent for humans.
Survival and multiplication of Brucella organisms in phagocytic cells are features essential to the establishment, development, and chronicity of the disease. The mechanisms by which brucellae avoid intracellular killing are not completely understood. Brucella spp. can change from a smooth to a rough colonial morphology based on the composition of their cell wall lipopolysaccharide O-side chain (LPS); those with a smooth LPS are more resistant to intracellular killing by neutrophils than those with a rough LPS. The smooth phenotype has been identified in B. abortus and B. melitensis. Brucellae ensure intracellular survival by interfering with the phagosome lysosome fusion in macrophages and epithelial cells. In addition, as do Legionella spp., brucellae use a type IV secretion system, VirB, for intracellular survival and replication. Unlike Legionella spp., however, brucellae modulate phagosome transport to avoid being delivered to lysosomes. Essentially, VirB is involved in controlling the maturation of the Brucella vacuole into an organelle that allows replication. In the mouse model, if mutations occur in this gene region, B. abortus is unable to establish chronic infections. In addition, Brucella spp. produce urease, which provides protection during passage through the digestive system when the organism is ingested in food products. Urease breaks down urea, producing ammonia, and neutralizes the gastric pH. Despite our current knowledge, many questions remain about the pathogenesis of disease caused by Brucella spp.
