The Fungi of Medical Importance

Fungi as Infectious Agents

• Fungi include mushrooms, shelf fungi, molds, and yeasts.
• They are ubiquitous and widely distributed in the air, dust, fomites, and part of our normal microbiota.
• Most fungi are nonpathogenic or cause mild infections.
• Mycosis = human fungal disease due to a true or opportunistic pathogen

Representative Fungal Pathogens

• Primary True Pathogens
  • Histoplasma capsulatum
    • Disease/Infection: Histoplasmosis
    • Primary Habitat and Distribution: Soils high in bird guano; Ohio and Mississippi valleys of United States; Mexico; Central and South America; Africa
  • Blastomyces dermatitidis
    • Disease/Infection: Blastomycosis
    • Presumably soils, but isolation has been difficult; southern Canada; Midwest, Southeast, Appalachia in United States; along drainage of major rivers
  • Coccidioides immitis & Coccidioides posadasii
    • Disease/Infection: Coccidioidomycosis
    • Highly restricted to alkaline desert soils in southwestern United States (California, Arizona, Texas, and New Mexico)
  • Paracoccidioides brasiliensis
    • Disease/Infection: Paracoccidioidomycosis
    • Soils of rain forests in South America (Brazil, Colombia, Venezuela)
• Pathogens with Intermediate Virulence
  • Sporothrix schenckii
    • Disease/Infection: Sporotrichosis
    • In soil and decaying plant matter; widely distributed
  • Genera of dermatophytes (Microsporum, Trichophyton, Epidermophyton)
    • Disease/Infection: Dermatophytosis (various ringworms or tineas)
    • Human skin, animal hair, soil throughout the world
• Secondary Opportunistic Pathogens
  • Candida albicans
    • Disease/Infection: Candidiasis
    • Normal flora of human mouth, throat, intestine, vagina; also normal in other mammals, birds; ubiquitous
  • Aspergillus spp.
    • Disease/Infection: Aspergillosis
    • Soil, decaying vegetation, grains; common airborne contaminants; extremely pervasive in environment
  • Cryptococcus neoformans
    • Disease/Infection: Cryptococcosis
    • Pigeon roosts and other nesting sites (buildings, barns, trees); worldwide distribution
  • Pneumocystis jirovecii
    • Disease/Infection: Pneumocystis pneumonia (PCP)
    • Upper respiratory tract of humans, animals
  • Genera in Mucorales (Rhizopus, Absidia, Mucor)
    • Disease/Infection: Mucormycosis
    • Soil, dust; very widespread in human habitation
• Specific mycotic infections are usually named by adding -mycosis, -iasis, or -osis to the generic name of the pathogen.

True Pathogens Characteristics

• Restricted to certain endemic regions
• Infection occurs when soil or other matter is disturbed, and spores are inhaled
• Spores germinate in lungs into yeasts to produce asymptomatic or mild primary pulmonary infection
• Systemic and creates severe, chronic lesions

True Pathogens: Dimorphism

• Natural Habitat: Saprobic (free-living)
  • Mycelial phase
  • Temperature (<30°C)
  • Reproduction through sporulation
• Animal Habitat: Parasitic
  • Yeast phase
  • Temperature (35°C–40°C)
  • Reproduction through budding or endospores
• When fungal spores from the environment gain entrance to a warm-blooded animal, they germinate into yeasts and remain in this phase in the host.
• Yeast cells leaving the animal host return to the environment and revert to the sporulating hyphal state.
• These conversions can be demonstrated on artificial media in the laboratory.
• Dimorphic = switch between hyphae/mycelia/mold phase to yeast/parasitic phase
• Thermal dimorphism

True Pathogens: Histoplasmosis (Ohio Valley Fever)

• Histoplasma capsulatum
• Thermal dimorphism.
  • growth at 25°C – white mycelium
  • growth at 37°C – creamy yeast colony
• Distribution: Ohio Valley and Mississippi Valley (and tributaries)
• Fungus grows best in moist soils high in nitrogen (ex: bird and bat guano)
• Allergic reaction to injection of histoplasmin into skin indicates its wide distribution in Ohio, Illinois, Missouri, Kentucky, Tennessee, Michigan, Georgia, and Arkansas.
• 80-90% of the population show signs of prior infection by age of 20.
• Spores disturbed in parks, bird roosting areas, old buildings
• Adult males make up majority of cases (higher levels of occupational exposure).
• Severe in immunocompromised.
• 500,00 cases per year – hospitalization or death
• ID = 5 spores from inhalation grows in alveolar macrophages
• Signs/Symptoms:
  • Mild: aches, pains, coughing
  • Severe: fever, night sweats, weight loss spread to brain, heart, liver, lymph nodes, bone marrow
  • Chronic pulmonary histoplasmosis =~tuberculosis

Histoplasmosis Infection Cycle

1. Mold with hyphae that produce spores
2. Disturbance disperses spores in air
3. Spores inhaled and travel to lungs
4. Warmer temperature transforms spores into yeasts
5. Yeast ingested by alveolar macrophages and transported to lymph nodes
6. Yeast travels to other parts of the body

Cutaneous Mycoses: Dermatophytosis

• Dermatophytosis = fungal infection of nonliving skin, hair, and nails
• aka: ringworm, tinea

Dermatophyte Genera and Diseases

• Infections from animals and soil are more severe than from humans.
• Not life-threatening, but pose serious health concerns due to extreme discomfort, stress, pain, and unsightliness.
• Fungal enzymes breakdown keratin as a nutrient in the skin, hair, and nails.

Types of Cutaneous Mycoses

• Tinea capitis (ringworm of the scalp) - common in kids
• Tinea barbae (ringworm of the beard) - aka: barber’s itch
• Tinea corporis (ringworm of the body)
• Tinea cruris (ringworm of the groin) - aka: jock itch
• Tinea pedis (ringworm of the foot) - aka: athlete’s foot

Opportunistic Mycoses: Candidiasis

• Candida albicans
• Normal microbiota in pharynx, genitalia, and skin; account for ~70% of fungal HAIs
• Onychomycosis – skin and nails
• Intertriginous – where moist skin rubs together (ex: armpits, groin, under breasts)
• Cutaneous candidiasis – burns, diaper rash
• Oral thrush – newborns and elderly
• Esophageal and anal infections – AIDS patients
• Vulvovaginal candidiasis (yeast infection) – women taking abx or pregnant
• “cottage cheese-like” discharge

Review Questions

1. The ability of a fungus to alternate between hyphal and yeast phases in response to temperature is a type of . b. dimorphism
2. Histoplasmosis has the greatest endemic occurrence in which United States region? c. midwest
3. Ringworm is caused by a . b. dermatophyte
4. Fungi are generally not transmitted from person to person. b. False
5. Treatment of women with antibiotics is a predisposing factor for the opportunistic fungal infection vulvovaginal candidiasis. a. True