Medical Mycology: Pathogenic Fungi

The Epidemiology of Mycoses

Mycoses are fungal diseases that arise from exposure to fungi and their spores in the environment. Understanding their epidemiology is crucial for diagnosis and prevention.

• Entry or Exposure Route: Inhalation is the most common route; trauma or ingestion is less frequent.

• Contagiousness: Most mycoses are not contagious; dermatophytes are an exception.

• True Pathogens: Only a few fungi are considered true pathogens; most are opportunistic.

• Clinical Manifestations:

  1. Fungal infections

  2. Fungal toxicosis

  3. Allergies

Examples of Systemic Mycoses: Histoplasmosis, Blastomycosis, Coccidioidomycosis

Antifungal Therapies

Challenges and Treatments

Mycoses are difficult to treat due to the similarity between fungal and human cells, leading to potential toxicity of antifungal drugs.

• Immune Evasion: Fungi often resist T cell-mediated immune responses.

• Drug Targets: Ergosterol in fungal membranes is a common target; however, cholesterol in human cells is similar, causing collateral damage.

• Amphotericin B: Gold standard but highly toxic.

• Less Toxic Alternatives: Ketoconazole, Itraconazole, Fluconazole.

Systemic Mycoses Caused by Pathogenic Fungi

Dimorphic Pathogenic Fungi

Pathogenic fungi in the division Ascomycota (e.g., Histoplasma, Blastomyces, Coccidioides, Paracoccidioides) exhibit dimorphism, changing form based on temperature.

• Environmental Form: Mycelial thalli at 30°C.

• Human Form: Spherical yeasts at 37°C.

• Transmission: Acquired through inhalation, leading to pulmonary infection and possible dissemination.

Histoplasmosis (Histoplasma capsulatum)

The most common fungal pathogen affecting humans, especially in the Eastern US, Africa, and South America.

• Ecology: Moist soils with high nitrogen; phagocytosed by macrophages in lungs.

• Clinical Forms:

  • Chronic pulmonary histoplasmosis

  • Chronic cutaneous histoplasmosis

  • Systemic histoplasmosis

  • Ocular histoplasmosis

• Diagnosis: Identification of yeast form in patient samples.

• Treatment: Amphotericin B or ketoconazole.

Blastomycosis (Blastomyces dermatitidis)

Endemic in the southeastern US and Canada, found in soils rich in organic matter.

• Pulmonary Blastomycosis: Most common, often asymptomatic but can become chronic.

• Cutaneous Blastomycosis: Painless lesions on face and upper body.

• Osteoarticular Blastomycosis: Spread to bones and joints.

• Meningitis: CNS involvement, especially in AIDS patients.

• Diagnosis: Fungi in culture or samples.

• Treatment: Amphotericin B or oral itraconazole; relapse common in AIDS patients.

Coccidioidomycosis (Coccidioides immitis)

Endemic to Southwestern US and Northern Mexico, associated with desert soils and rodent burrows.

• Transmission: Inhalation of arthroconidia, which germinate into spherules in the lung.

• Clinical Manifestations: Pulmonary conditions, often mild or asymptomatic; dissemination in immunocompromised.

• Diagnosis: Spherules in patient samples or positive skin test.

• Treatment: Amphotericin B; maintenance therapy for AIDS patients.

• Prevention: Protective masks in endemic areas.

Paracoccidioidomycosis (Paracoccidioides brasiliensis)

Found in southern Mexico and South America, mostly affecting farm workers.

• Clinical Features: Pulmonary infection, can spread and create lesions.

• Diagnosis: "Steering wheel" formation of yeast buds in samples.

• Treatment: Itraconazole, ketoconazole, or amphotericin B.

Opportunistic Mycoses

Predisposing Factors (Table 22.1)

Opportunistic mycoses occur in individuals with compromised immunity or disrupted microbiome.

Pneumocystis Pneumonia (Pneumocystis jiroveci)

Common in AIDS patients; most individuals exposed by age five.

• Transmission: Inhalation

• Clinical Features: Asymptomatic in healthy; diagnostic for AIDS; can be fatal if untreated.

• Diagnosis: Clinical and microscopic findings.

• Treatment: Trimethoprim and sulfamethoxazole.

Candidiasis (Candida albicans)

Opportunistic infection of skin and mucous membranes; common microbiota.

• Diagnosis: Clusters of budding yeasts and pseudohyphae.

• Treatment: Nystatin, azole suppositories/creams, fluconazole; difficult to treat in AIDS patients.

Aspergillosis (Aspergillus spp.)

Environmental fungi causing allergies and pulmonary diseases.

• Hypersensitivity Aspergillosis: Asthma-like symptoms.

• Noninvasive Aspergillomas: Fungal masses in lung cavities.

• Acute Invasive Pulmonary Aspergillosis: May present as pneumonia.

• Cutaneous/Systemic Aspergillosis: Occurs in immunocompromised.

• Treatment: Allergy medications, surgical removal, intravenous voriconazole.

Cryptococcosis (Cryptococcus neoformans)

Results from inhalation of spores or dried yeast in bird droppings; important in immunocompromised patients.

• Pathogenic Features: Resists phagocytosis, CNS predilection.

• Clinical Forms:

  • Primary pulmonary cryptococcosis

  • Cryptococcal meningitis

  • Cryptococcoma

  • Cutaneous cryptococcosis

• Diagnosis: Identification in patient sample.

• Treatment: Amphotericin B and 5-fluorocytosine; fluconazole for maintenance in AIDS patients.

Superficial Mycoses

Dermatophytoses (Trichophyton spp.)

Most common fungal infections, confined to outer dead layers of skin, nails, or hair (keratin-rich).

• Agents: Genera of ascomycetes; previously called ringworms.

• Transmission: Person-to-person; may trigger immune response damaging living tissue.

• Diagnosis: Identification of hyphae or arthroconidia in samples.

• Treatment: Topical terbinafine; oral antifungals for widespread infection.

Fungal Intoxications and Allergies

Mycotoxicosis and Mycetismus

Some fungi produce toxins or cause allergies, leading to toxicosis or hypersensitivity reactions.

• Mycotoxicosis: Caused by eating mycotoxins (e.g., aflatoxins from Aspergillus).

• Mycetismus: Mushroom poisoning from ingestion of toxic fungi.

• Allergic Reactions: Fungal allergens can elicit hypersensitivity responses in sensitive individuals.