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Microbiology

Dimorphic Fungi

Those shape-shifting organisms that can exist as molds in the environment and as yeasts or spherules in the body! We’ll cover the major players: Histoplasma capsulatum, Blastomyces, Coccidioides, and Sporothrix schenckii, focusing on their disease states, how they spread, and how we identify them in the lab

Dimorphic Fungi

  • Definition: Dimorphic fungi are those that exhibit two distinct morphological forms depending on environmental conditions, primarily temperature
    • Mold Form: In the environment (soil, decaying vegetation), they grow as filamentous molds with hyphae and conidia
    • Tissue Form: In the human body (at body temperature), they transform into a different form, typically yeasts or spherules
  • Infection Mechanism: Humans typically acquire these infections by inhaling the mold form’s conidia from the environment
  • Geographic Distribution: Each dimorphic fungus has a characteristic geographic distribution, which is important to consider when evaluating patients
  • Key Genera: We’ll focus on Histoplasma, Blastomyces, Coccidioides, and Sporothrix, which are the most clinically significant dimorphic fungal pathogens

Histoplasma capsulatum

  • Etiology: Histoplasma capsulatum is the causative agent of histoplasmosis
  • Epidemiology
    • Found worldwide, but most common in the Ohio and Mississippi River valleys in the United States, as well as parts of Central and South America, Africa, and Asia
    • Grows in soil enriched with bird or bat droppings (e.g., caves, old buildings, chicken coops)
    • Infection occurs through inhalation of conidia from disturbed soil
    • Risk factors for severe disease:
      • Immunosuppression (HIV/AIDS, organ transplantation, TNF-alpha inhibitors)
      • Infancy
      • Advanced age
  • Transmission
    • Not transmitted from person to person
    • Acquired through inhalation of conidia from the environment
  • Disease States
    • Asymptomatic Infection: Most individuals exposed to Histoplasma are asymptomatic or have mild, self-limited symptoms
    • Acute Pulmonary Histoplasmosis: Flu-like illness with fever, cough, chest pain, and fatigue. Can resemble pneumonia
    • Chronic Pulmonary Histoplasmosis: Progressive lung infection that resembles tuberculosis, often seen in patients with underlying lung disease (e.g., COPD)
    • Disseminated Histoplasmosis: Spread of the infection to multiple organs, including the liver, spleen, bone marrow, and lymph nodes. More common in immunocompromised individuals
    • Progressive Disseminated Histoplasmosis: Severe, life-threatening form of disseminated histoplasmosis, characterized by fever, weight loss, hepatosplenomegaly, and pancytopenia
  • Laboratory Diagnosis
    • Specimen Collection
      • Respiratory: Sputum, bronchoalveolar lavage (BAL), lung biopsy
      • Blood: For disseminated infection
      • Bone Marrow: For disseminated infection
      • Urine: For antigen detection
      • Tissue Biopsies: Liver, spleen, lymph nodes
    • Direct Microscopic Examination
      • Wright-Giemsa stain of bone marrow or blood smears to visualize small, intracellular yeasts within macrophages
      • GMS (Gomori Methenamine Silver) or PAS (Periodic Acid-Schiff) stain of tissue biopsies to highlight fungal elements
    • Culture
      • Inoculation onto SDA (Sabouraud Dextrose Agar) or BHI (Brain-Heart Infusion) agar
      • Incubation at 25-30°C (mold form) and 35-37°C (yeast form)
      • Mold form: White to brown, cottony colonies
      • Yeast form: Smooth, creamy colonies
    • Identification
      • Mold Form: Microscopic examination of the mold form reveals characteristic tuberculate macroconidia (large, thick-walled conidia with knob-like projections)
      • Yeast Form: Small, oval yeast cells (2-4 μm) that reproduce by budding
      • MALDI-TOF MS: Rapid and accurate identification
      • Molecular Methods: PCR and sequencing for definitive identification
    • Antigen Detection
      • Histoplasma Antigen Assay: Detects Histoplasma antigen in urine or serum. A useful test for diagnosing histoplasmosis, especially disseminated disease
    • Antibody Detection
      • Histoplasma Antibody Test: Detects antibodies against Histoplasma in serum. Can be helpful, but may have cross-reactivity with other fungal infections

Blastomyces dermatitidis

  • Etiology: Blastomyces dermatitidis is the causative agent of blastomycosis
  • Epidemiology
    • Found primarily in North America, particularly in the southeastern and midwestern United States and southern Canada
    • Also found in parts of Africa, Asia, and South America
    • Grows in moist soil and decaying organic matter near waterways
    • Infection occurs through inhalation of conidia from disturbed soil
    • Risk factors for severe disease:
      • Immunosuppression
      • Diabetes
      • Alcoholism
      • Pregnancy
  • Transmission
    • Not transmitted from person to person
    • Acquired through inhalation of conidia from the environment
  • Disease States
    • Pulmonary Blastomycosis: Lung infection, ranging from asymptomatic to pneumonia. Symptoms include cough, fever, chest pain, and weight loss
    • Disseminated Blastomycosis: Spread of the infection to other organs, including the skin, bones, genitourinary tract, and central nervous system
    • Cutaneous Blastomycosis: Skin lesions, often verrucous (wart-like) or ulcerated
    • Osteomyelitis: Bone infection
    • Central Nervous System Blastomycosis: Meningitis or brain abscess
  • Laboratory Diagnosis
    • Specimen Collection
      • Respiratory: Sputum, bronchoalveolar lavage (BAL), lung biopsy
      • Skin: Biopsy of skin lesions
      • Bone: Bone biopsy
      • Urine: For antigen detection
      • Tissue Biopsies: From affected organs
    • Direct Microscopic Examination
      • KOH preparation or Gram stain of sputum or tissue samples to visualize large, thick-walled yeast cells with broad-based budding
      • GMS or PAS stain of tissue biopsies to highlight fungal elements
    • Culture
      • Inoculation onto SDA or BHI agar
      • Incubation at 25-30°C (mold form) and 35-37°C (yeast form)
      • Mold form: White to brown, fluffy colonies
      • Yeast form: Creamy, wrinkled colonies
    • Identification
      • Mold Form: Microscopic examination of the mold form reveals small, oval conidia on short conidiophores (“lollipop” appearance)
      • Yeast Form: Large, round yeast cells (8-15 μm) with thick walls and broad-based budding
      • MALDI-TOF MS: Rapid and accurate identification
      • Molecular Methods: PCR and sequencing for definitive identification
    • Antigen Detection
      • Blastomyces Antigen Assay: Detects Blastomyces antigen in urine or serum. A useful test for diagnosing blastomycosis
    • Antibody Detection
      • Blastomyces Antibody Test: Can be helpful, but may have cross-reactivity with other fungal infections

Coccidioides immitis and Coccidioides posadasii

  • Etiology: Coccidioides immitis and Coccidioides posadasii are the causative agents of coccidioidomycosis (Valley Fever)
  • Epidemiology
    • Found primarily in the southwestern United States (California, Arizona, New Mexico, Texas) and parts of Mexico and South America
    • Grows in arid and semi-arid soil
    • Infection occurs through inhalation of arthroconidia (a type of fungal spore) from disturbed soil
    • Risk factors for severe disease:
      • Immunosuppression
      • Pregnancy
      • African American or Filipino ethnicity
      • Diabetes
  • Transmission
    • Not transmitted from person to person
    • Acquired through inhalation of arthroconidia from the environment
  • Disease States
    • Asymptomatic Infection: Most individuals exposed to Coccidioides are asymptomatic or have mild, self-limited symptoms
    • Acute Pulmonary Coccidioidomycosis: Flu-like illness with fever, cough, chest pain, and fatigue. Can resemble pneumonia
    • Chronic Pulmonary Coccidioidomycosis: Persistent lung infection with nodules, cavities, or bronchiectasis
    • Disseminated Coccidioidomycosis: Spread of the infection to other organs, including the skin, bones, meninges, and joints
    • Coccidioidal Meningitis: A serious complication of disseminated coccidioidomycosis, characterized by headache, stiff neck, and altered mental status
  • Laboratory Diagnosis
    • Specimen Collection
      • Respiratory: Sputum, bronchoalveolar lavage (BAL), lung biopsy
      • CSF: For suspected meningitis
      • Skin: Biopsy of skin lesions
      • Bone: Bone biopsy
      • Tissue Biopsies: From affected organs
    • Direct Microscopic Examination
      • KOH preparation or Gram stain of sputum or tissue samples to visualize spherules (large, round structures containing endospores)
      • GMS or PAS stain of tissue biopsies to highlight fungal elements
    • Culture
      • Inoculation onto SDA or BHI agar
      • Incubation at 25-30°C (mold form)
      • Mold form: White to gray, fluffy colonies that produce abundant arthroconidia
      • Caution: Coccidioides cultures are highly infectious and should be handled with extreme care in a biosafety level 3 (BSL-3) laboratory
    • Identification
      • Mold Form: Microscopic examination of the mold form reveals barrel-shaped arthroconidia that alternate with empty cells
      • Tissue Form: Large, round spherules (20-60 μm) containing numerous endospores
      • Molecular Methods: PCR and sequencing for definitive identification
    • Antibody Detection
      • Coccidioides Antibody Test: Detects IgM and IgG antibodies against Coccidioides in serum. A key diagnostic test for coccidioidomycosis
      • Complement Fixation (CF) Test: Measures IgG antibodies and is used to monitor disease progression and response to treatment

Sporothrix schenckii

  • Etiology: Sporothrix schenckii is the causative agent of sporotrichosis (Rose Gardener’s Disease)
  • Epidemiology
    • Found worldwide
    • Grows in soil, decaying vegetation, and sphagnum moss
    • Infection occurs through traumatic inoculation of the skin (e.g., a thorn prick)
    • Occupational risk factors: Gardeners, farmers, florists, forestry workers
  • Transmission
    • Not transmitted from person to person
    • Acquired through traumatic inoculation of the skin with conidia or hyphal fragments
  • Disease States
    • Cutaneous Sporotrichosis
      • The most common form of sporotrichosis
      • Characterized by a painless nodule at the site of inoculation, followed by the development of secondary nodules along the lymphatic vessels
    • Lymphocutaneous Sporotrichosis
      • Infection spreads along the lymphatic vessels, causing a chain of nodules
    • Disseminated Sporotrichosis
      • Rare, but can occur in immunocompromised individuals
      • Infection spreads to other organs, including the lungs, bones, joints, and central nervous system
    • Pulmonary Sporotrichosis
      • Rare, but can occur through inhalation of conidia
  • Laboratory Diagnosis
    • Specimen Collection
      • Skin Biopsy: From the nodule or ulcer
      • Aspirate: From the nodule
      • Sputum: For suspected pulmonary infection
      • Synovial Fluid: For suspected joint infection
      • Tissue Biopsies: From affected organs
    • Direct Microscopic Examination
      • Difficult to visualize in tissue samples
      • GMS or PAS stain of tissue biopsies to highlight fungal elements
    • Culture
      • Inoculation onto SDA or BHI agar
      • Incubation at 25-30°C (mold form) and 35-37°C (yeast form)
      • Mold form: Initially white, becoming dark brown or black with age
      • Yeast form: Creamy, white to tan colonies
    • Identification
      • Mold Form: Microscopic examination of the mold form reveals delicate, hyaline hyphae with oval conidia arranged in a rosette-like pattern at the tips of conidiophores
      • Yeast Form: Small, round or oval yeast cells (3-5 μm)
      • MALDI-TOF MS: Rapid and accurate identification
      • Molecular Methods: PCR and sequencing for definitive identification

Key Takeaways

  • Dimorphic fungi are a unique group of pathogens that can cause a variety of infections, ranging from localized skin conditions to life-threatening disseminated diseases
  • Accurate identification of dimorphic fungi is crucial for guiding appropriate antifungal therapy
  • Laboratory diagnosis involves a combination of direct microscopic examination, culture, and molecular methods
  • Serologic tests (antigen and antibody detection) can be helpful in diagnosing certain dimorphic fungal infections

Key Terms

  • Dimorphism: The ability of a fungus to exist in two different morphological forms (mold and yeast/spherule) depending on environmental conditions
  • Conidia: Asexual spores produced by fungi
  • Arthroconidia: A type of asexual spore formed by the fragmentation of hyphae, characteristic of Coccidioides
  • Spherule: A large, round structure containing endospores, formed by Coccidioides in infected tissues
  • Tuberculate Macroconidia: Large, thick-walled conidia with knob-like projections, characteristic of Histoplasma capsulatum
  • Broad-Based Budding: A type of budding in which the bud has a wide base of attachment to the parent cell, characteristic of Blastomyces dermatitidis
  • Rose Gardener’s Disease: A common name for sporotrichosis, due to the association with traumatic inoculation of the skin with Sporothrix schenckii from rose thorns or other plants
  • Lymphocutaneous Sporotrichosis: Sporotrichosis that spreads along the lymphatic vessels, causing a chain of nodules
  • Antifungal Susceptibility Testing: Laboratory tests to determine the susceptibility of fungi to antifungal drugs
  • Itraconazole: A triazole antifungal drug commonly used to treat histoplasmosis, blastomycosis, and sporotrichosis
  • Amphotericin B: A polyene antifungal drug used to treat severe or disseminated dimorphic fungal infections
  • Voriconazole: A triazole antifungal drug used to treat coccidioidomycosis and other fungal infections
  • Arthroconidia: A type of asexual spore formed by the fragmentation of hyphae. Coccidioides immitis produces arthroconidia in its mold form
  • Spherule: A large, spherical structure containing endospores, formed by Coccidioides immitis in infected tissues