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, american bishop 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.[1]
  • 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.[2]

Microscopic Pathology

Brucella spp. are poorly staining, small gram-negative coccobacilli (0.5-0.7 x 0.6-1.5 µm), and are seen mostly as single cells and appearing like “fine sand”.
Histopathology of guinea pig liver in experimental Brucella suis infection. Granuloma with necrosis
  • 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”.[3]
  • On microscopic histopathological analysis of the liver, common findings are:
    • Granulomas with centrilobular necrosis or focal necrosis and parenchyma destruction.[4]

Reference

  1. Brucellosis. CDC. http://www.cdc.gov/brucellosis/transmission/index.html. Accessed on January 29, 2016
  2. Corbel MJ (1997). "Brucellosis: an overview". Emerg Infect Dis. 3 (2): 213–21. doi:10.3201/eid0302.970219. PMC 2627605. PMID 9204307.
  3. Brucellosis. Wikipedia. https://en.wikipedia.org/wiki/Brucellosis. Accessed on January 29, 2016
  4. Hunt A, Bothwell P. Histological findings in human brucellosis. J Clin Pathol. 1967; 20: 267-272

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