Diseases caused by fungal infections

The silent crisis: Fungal infections

Pathogenesis of fungal infections

1. Opportunistic growth
2. Tissue damage
3. Virulence factors
   1. Capsule (Cryptococcus)
   2. Keratinase
4. Inflammatory immune response

Host defenses

• Primarily cell-mediated
• TH1 - cytokines
• Inflammation
• IFN-gamma: activate macrophages

Antifungal treatment

1. Topical
2. Systemic: amphothericin B, fluorocytosine

Types of fungal infections

1. Superficial: Hair and skin surface
2. Cutaneous: keratinized tissue
3. Subcutaneous: more invasive
4. Systemic

Diseases caused by fungi

1. Superficial mycoses
   1. Growth of fungi on surface of skin or hair
   2. Clinical conditions
      • Pytiriasis versicolor (Malassezia furfur)
      • Tinea nigra
      • Black or white piedra (hair)
2. Cutaneous mycoses
   1. Often called ringworm (Tinea)
   2. Typically caused by 3 groups of molds
      • Microsporum
      • Epidermophyton
      • Trichophyton
   3. May be carried by humans, animals or found in soil
3. Subcutaneous mycoses
   1. More invasive and destructive
   2. Elicit immune reaction
   3. Sometimes difficult to treat; may require surgery or amputation
   4. Clinical diseases
      1. Sporotrichosis
         • Cause: Sporothrix schenckii
         • Trauma/wound entry of spores
         • Ulcering lesions along lymphatic duct affected
      2. Chromoblastomycosis
         • Cause: various pigment-producing fungi
         • Warty, cauliflower-like skin lesions
      3. Eumycotic mycetoma
         • Several types of fungi
      4. Subcutaneous zygomycosis
         • Conidiobolus and Basidiobolus
         • Extensive swelling in affected area
      5. Subcutaneous Phaeohyphomycosis
         • Dematiacious fungi (e.g. Phialophora, Exophiala)
         • single cyst; may expand to cover more body surfaces
         • systemic infection occurs in immunocompromised patients
4. Systemic mycoses
   1. Caused by virulent fungi
   2. Can cause disease in healthy individuals
   3. Can evade host defenses
   4. Many of these fungi are dimorphic
      • Mold phase found in nature
      • Yeast phase is pathogenic stage
   5. Clinical Diseases

Histoplasmosis

1. Cause: Histoplasma capsulatum
2. Endemic in Midwestern US
3. Associated with bats and birds
4. Pneumonia in 5% of infected
5. Disseminated progressive disease (immunocompromised)

Blastomycosis

1. Cause: Blatomyces dermatitidis
2. Endemic in North America
3. Associated with dogs
4. Primary infection is usually asymptomatic
5. Blastomyces can survive in macrophages = dissemination
6. Pulmonary disease
7. Disseminated disease with bone and brain lesions

Coccidiomycosis (San Joaquin Valley Fever)

1. Cause: Coccidioides immitis
2. Endemic in the Americas
3. Associated with arid soil
4. ~ 40% of infections are symptomatic: benign respiratory
   • cough, fever, chest pain
5. Progressive disease in lungs
6. Systemic disease involves skin & meninges

Paracoccidiomycosis

1. Cause; Paracoccidioides braziliensis
2. Dimorphic yeast/mold
3. Limited to South America
4. Inhalation of spores
5. Usually self-limiting, but disease may remain dormant and reactivate later
6. Infection can spread to multiple tissues and organs

Opportunistic mycoses

Cryptococcosis

1. Cause: Cryptococcus neoformans
2. Encapsulated yeast
3. Associated with pigeons
4. Fungal meningitis & disseminated disease in AIDS
5. Lung infection leads to nodule formation
6. Meningitis (headache, fever, mental changes)
7. Skin and bone lesions

Candidiasis

1. Causes: Candida albicans et al.
2. Primarily a problem in the compromised host
   • Wounds
   • Antimicrobial drugs
   • Immunosuppression
   • AIDS
3. External candidiasis: Thrush, vaginosis
4. Chronic candidiasis: Drug-resistant mucocutaneous candida
5. Systemic candidiasis: various organs, incl. brain
   • not a big problem in AIDS

Aspergillosis

1. Cause: Aspergillus flavus and A. fumigatus
2. Food intoxication (aflatoxin)
3. Hypersensitivity pulmonary disease (allergic reaction)
4. Colonization
5. Systemic disease (invasive)
6. Hyphal growth in blood vessels and tissues
7. Blockage of blood vessels by hyphae and clots
8. Tissue necrosis

Zygomycosis

1. Cause: Rhizopus, Mucor
2. Rhinocerebral zygomycosis: sinuses, eyes, palate, brain
   • terminally acidotic/diabetic patients
3. Colonization of other organs and tissues
4. Dissemination with growth in major blood vessels

Pneumocystis pneumonia

1. Cause: Pneumocystis jirovecii
2. Common in old age, immunosuppression, and AIDS
3. Common in human population (asymptomatic) and rats
4. Causes interstitial pneumonitis, fever, cyanosis
5. Resistant cysts formed

Unusual infections

1. Adiaspiromycosis (Fig. 1)
   1. Emmonsia spp.
   2. causes granulomas in lungs
2. Lobomycosis (Fig. 2)
   • Chronic cutaneous infection (nodules) caused by Lacazia loboi
   • South/central Americas; also found in dolphins
3. Chlorellosis (Fig. 3)
   1. Caused by green algae
   2. usually sheep/cattle infection
4. Protothecosis (Fig. 4)
   • chloroplast-less algae (Prototheca wickerhamii)
   • skin nodules; usually in immunocompromised
5. Pythiosis insidiosis (Fig. 5)
   1. Caused by protist microbe Pythium insidiosis (oomycete)
   2. Ischemia and tissue necrosis in lower limbs; usually a veterinary disease