Human fungal infections 1

• Describe mycotoxicoses

  This is a disease caused by mycotoxins, which are small organic metabolites produced by fungi which exert toxic effects on animals and humans. These include penicillin, gliotoxin and aflatoxin, which is carcinogenic. Symptoms of mycotoxicoses:

  • Breathing problems
  • Dizziness
  • Hallucination
• Describe how mycoses are classified

  Mycoses are classified by the level of tissue affected:

  • 60 species can infect humans
  • C. albicans: this is an opportunistic pathogen that causes infection commonly in women
• Describe candida albicans

  This is a single cell fungal morphotype known as budding yeast that can differentiate into both pseudohyphal and or hyphal forms in response to: pH, nutrient limitation and serum.
• Describe Aspergillus niger

  This is a filamentous sporulating fungi that distributes its sports via air currents to inhabit new food sources. In favourable conditions, these spores germinate into hyphae, which branch and at their ends forms structures bearing the spores, named conidiophores. A fungal colony composed of multiple branched hyphae is referred to as a mycelium. These are commonly known as moulds.
• What are dimorphic fungi?

  These are fungi that are capable of changing morphology in response to temperature changes. Example: Blastomyces dermatidis:

  • 25 degrees C: filamentous
  • 37 degrees C: budding
• What is the difference between opportunistic and primary pathogens?

  Opportunistic: these pathogens require an immunocompromised host in order to establish infection. They are usually ubiquitous across populations and an example includes Candida albicans.

  Primary: these pathogens are able to establish an infection in a normal host. They usually have well defined geographical areas and an example incudes Blastomyces dermatiditis.
• Describe the immune cells that underpin anti-fungal responses

  Innate immunity: macrophages, neutrophils and dendritic cells exhibit anti-microbial activity and phagocytosis with oxidative and non-oxidative killing. They also secrete pro-inflammatory cytokines and chemokines whilst presenting antigens to T and B cells.

  Adaptive immunity: B cell and CD8 T cells mediate microbe killing.
• Describe the different risk factors for opportunistic mycoses

  • Candida (mucosal infection): impaired cell mediated immunity, e.g., AIDs
  • Candida (disseminated infection): breach of epithelial layer (surgery) and neutrophil depletion (chemotherapy)
  • Aspergillus: neutrophil depletion and high dose corticosteroids (organ transplant)
  • Cryptococcus: impaired cell mediated immunity and corticosteroids
• Describe the current challenges in fighting fungal diseases

  • Mostly the result of opportunistic pathogens
  • Airborne sources of infection
  • Poor diagnostics
  • Few antifungal therapies
  • Resistance to current antifungals
  • No antifungal vaccines due to the alterations in morphology of fungus with changing conditions
• Describe current antifungal drugs

  Only 4 classes of antifungal drugs used to treat systemic fungal infections:

  • Triazoles: these are used as a first line treatment and bind to fungal cytochrome P450, leading to disruption of fungal membranes, e.g., Fluconazole
  • Echinocandins: inhibit cell wall formation, e.g., micafungin
  • Polyenes: bind to fungal cell membranes and form pores, leading to osmotic lysis. One example is amphotericin B, which has a range of side effects and poor deliver to the site of infection.
  • 5-fluorocytosine: has anti-mycotic activity but is not widely available
• Describe resistance to drugs

  This is the inherited ability of microorganisms to grow at high concentrations of an antibiotic. This can be intrinsic (primary resistance where organisms are naturally resistant to a drug) or acquired (where resistance is acquired due to exposure to a drug).