MICROBIOLOGY

• Paracoccidioides species
  • P. brasiliensis (also known as S1a and S1b), P. americana (PS2), P. restrepiensis (PS3), P. venezuelensis (PS4), P. lutzii, P. lobogeorgii and P. ceti (causes disease in dolphins)
• Geographic distribution:
  • Most cases occur in Brazil, but the range is as far north as Mexico.
    • P. brasiliensis, P. americana (PS2) and P. lutzi: found across South America.
    • P. restrepiensis and P. venezuelensis: found in Colombia and Venezuela, respectively.
    • Significant differences in annual incidence rates were reported among Brazilian states (range 0.7 to 40 cases per 100,000 inhabitants)[2].
• Ecological associations: Mostly in rural and peri-urban environments.
  • Humid, rainy, forested areas near rivers
  • Agricultural (mainly coffee and tobacco crops)
  • Armadillo hunting
  • Large-scale construction projects (e.g., hydroelectric dams) that disturb soil.
• Morphology (dimorphic nature)
  • The mycelium phase (mold) is the form found in the environment and when samples are cultured at 25C. Hyphae and conidia.
  • Yeast phase: This is the form found in tissues and body fluids and when samples are cultured at 37C
    • Microscopic appearance is of a large parent cell with multiple budding yeasts [Fig 1] emerging from it to create the characteristic ship’s wheel appearance [Fig 2].
• Pathogenesis:
  • Infectious propagules (conidia) produced by the environmental mycelium phase are inhaled by accidental hosts (humans and armadillos are the main ones).
  • The transition from the conidia to the yeast phase occurs in the lungs.
    
    • Most infected individuals will control infection with T cell-driven granuloma formation and will not develop clinical disease.
    • The acute/subacute (“juvenile”) form occurs in children and young adults whose T cell responses cannot control the infection.
      • Occurs weeks to months after initial exposure.
    • Chronic (“adult”) form: >80% of cases
      • Quiescent fungus in granuloma that had previously been controlled becomes active long after the initial infection.
    • Predisposing factors:
      • Gender: The male-to-female ratio is ~22:1. One reason is that circulating estrogens inhibit the transformation of the aspirated conidia into yeast cells.
      • Genetic variables: specific MHC antigens (HLA-A9, HLA-B13 and C4B*-Q0) and the IL12RB1 641AA genotype are associated with risk for developing the disease.