Mycology II- Opportunistic Fungi

Question 1

1. Identify the defects in host defenses and describe how these factors lead to increased susceptibility to fungal infection. (9 with examples)

Answer 1

1. compromise of skin barrier by burns or traumatic wounds, may also require diminished CMI (airborne, soil or nosocomial infection)
2. reduction or alteration of normal flora (antibiotics, hormonal variation or foreign substance)
3. inherited immunodeficiency (chronic granulomatous disease, SCID etc.)
4. cancer- lymphohematologic malignancies
5. cytotoxic or immunosuppressive chemotherapy or radiation (ie. inflammatory tx or post transplant) – causing neutropenia
6. immunosupressive drugs: steroids, TNFa (infliximab, etanercept) inhibitors, etanercept, calcineurin inhibitors (cyclosporin A and tacrolimus), mycophenolate mofetil
7. nosocomial infection: immunocompromise, antibiotic use, invasive procedures and exposure
8. extremes of age
9. Other infections- immunomodulating: CMV, EBV, HIV
10. diabetes: disordered physiologic homeostasis and cellular response deficiencies, compromised microvascular, acidosis (free iron)

Question 2

2. Identify the environmental ecological niches, geographic distribution, environmental and photogenic tissue foams and routes of infection for Cryptococcus neoformans.

Answer 2

yeast with a capsule GXM, not a strict opportunist

worldwide and ubiquitous in the environment, particularly with guano from birds

C. neoformans v. grubii (A)
C. neoformans v. neoformans (D)
C. neoformans v. gattii (B and C)

Question 3

3. Describe the most common clinical manifestation of cryptococcal infection.

Answer 3

exposure to respiratory and GI tract, penetration of small airways by sexual spores (conidia) and extra-cellular infection that can disseminate

pulmonary infection resulting in diffuse interstitial pneumonia, pleural effusion and acute respiratory distress syndrome

disseminated: meningitis (**encapsulated), fungemia, skin and prostate

major cause of morbidity for AIDS patients (6-12%) improved with ART

Question 4

4. Identify cryptococcal polysaccharide capsule and melanin as virulence determinants and describe a potential pathogenic mechanism of each.

Answer 4

virulence factors:

capsule (of GXM, GalXM and mannoprotein), antibodies against are used for serotyping– antiphagocytic, depletion of complement component and down modulates immune response (***capsule is environmentally regulated- CO2 concentration, iron deprivation )

phenoloxidase uses phenoloxidase substrates in CNS to make quinones- melanins: act as free radical scavengers, physical or chemical barrier protection (environmental toughness)

growth at 37C

Question 5

How do you diagnose cryptococcal infection.

Answer 5

cryptococcal antigen (latex agglutination test) on CSF or serum looking for antigens to capsular polysaccharide- most sensitive

india ink test on CSF, visualize particles

culture of CSF or blood (slow and not sensitive)

microscopic tissue histology: “soccer ball” appearance of encapsulated yeast

Question 6

What is the tx. for cryptococcal infection?

Answer 6

life threatening infection: amphotericin B and 5-flucytosine

fluconazole to finish treatment or for long-term suppressive therapy or as a first time drug in less severe infection or in prophylaxis