Brucellosis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2] Danitza Lukac

Pathophysiology

Transmission

• Brucella spp. are primarily passed among animals, and they cause disease in many different vertebrates.
• Various Brucella species affect sheep, goats, cattle, deer, elk, pigs, dogs, and several other animals.
• Humans are generally infected in one of three ways:
  • Eating undercooked meat or consuming unpasteurized/raw dairy products
    • The most common way to be infected is by eating or drinking unpasteurized/raw dairy products.
    • When sheep, goats, cows, or camels are infected, their milk becomes contaminated with the bacteria.
    • If the milk from infected animals is not pasteurized, the infection will be transmitted to people who consume the milk and/or cheese products.
  • Breathing in the bacteria that cause brucellosis (inhalation)
    • This risk is generally greater for people in laboratories that work with the bacteria.
    • Slaughterhouse and meat-packing employees have also been known to be exposed to the bacteria and ultimately become infected.
  • Bacteria entering the body through skin wounds or mucous membranes
    • Bacteria can also enter wounds in the skin/mucous membranes through contact with infected animals.
    • This poses a problem for workers who have close contact with animals or animal excretions (newborn animals, fetuses, and excretions that may result from birth).
    • Such workers may include:
      • Slaughterhouse workers
      • Meat-packing plant employees
      • Veterinarians
• Person-to-person spread of brucellosis is extremely rare.
• Infected mothers who are breast-feeding may transmit the infection to their infants.
• Sexual transmission has been rarely reported.
• While uncommon, transmission may also occur via tissue transplantation or blood transfusions.
• Liver:

Pathogenesis

• Virulent Brucella organisms can infect both nonphagocytic and phagocytic cells.
• Within nonphagocytic cells, brucellae tend to localize in the rough endoplasmic reticulum.
• In polymorphonuclear or mononuclear phagocytic cells, they use a number of mechanisms for avoiding or suppressing bactericidal responses.
• The lipopolysaccharide of smooth phase strains (S-LPS) probably plays a substantial role in intracellular survival, as smooth organisms survive much more effectively than nonsmooth ones.
• S-LPS is the main antigen responsible for containing protection against infection in passive transfer experiments with monoclonal and polyclonal antibodies.
  • The protection is usually short-term and incomplete.
• The elimination of virulent Brucella depends on activated macrophages and hence requires development of Th1 type cell-mediated responses to protein antigens.
• An important determinant of virulence is the production of adenine and guanine monophosphate, which inhibit phagolysosome fusion; degranulation and activation of the myelo-peroxidase-halide system; and production of tumor necrosis factor.
• Survival within macrophages is associated with the synthesis of proteins of molecular weight 17, 24, 28, 60, and 62 kDa.
  • The 24 kDa protein is acid-induced, and its production correlates with bacterial survival under acidic conditions (<pH4).
  • The 17 and 28 kDa proteins are apparently specifically induced by macrophages and correlated with intracellular survival.
• High iron concentrations promote the killing of Brucella, probably by favoring production of hydroxylamine and hydroxyl radical.
• The mechanisms of pathogenesis of Brucella infection in its natural host species and in humans are still not completely understood, and further studies are needed.

Microscopic Pathology

• Brucella spp. are gram-negative in their staining morphology.
• Brucella spp. are poorly staining, small gram-negative coccobacilli (0.5-0.7 x 0.6-1.5 µm).
• Brucella spp. are seen mostly as single cells and appearing like “fine sand”.
• Liver:
  • Granulomas with centrilobular necrosis or focal necrosis and parenchyma destruction.