Systemic and Endemic Dimoprhic Mycoses

Eurotiomycetes (Phylum: Ascomycota)

Histoplasma capsulatum Taxonomic Class & Phylum

Histoplasma capsulatum

Thermally dimorphic fungus (mold at 25 °C, yeast at 37 °C)

Histoplasma capsulatum

Macroscopic:
• 25 °C (mold): White-to-buffy tan, silky to woolly colony with a pale-to-yellowish reverse.

Histoplasma capsulatum

Macroscopic:
• 37 °C (yeast): Cream-colored, smooth, moist yeast-like colony.

Histoplasma capsulatum

Microscopic:
• 25 °C (mold): Large, thick-walled, spherical tuberculate macroconidia with finger-like projections, accompanied by small, smooth microconidia.

Histoplasma capsulatum

Microscopic:
• 37 °C (yeast): Small, oval, single-budding yeast cells (2-4 µm), typically seen within macrophages.

Histoplasma capsulatum

Growth: Slow growth (2-4 weeks) at 25 and 37 °C

Histoplasma capsulatum

Transmission/Reservoir: Inhalation of microconidia; associated with soil enriched with bird or bat droppings (guano).

Histoplasma capsulatum

Risk Factors: Cave explorers (spelunkers), construction/demolition workers, HIV/AIDS patients (CD4 <150/µL).

Histoplasma capsulatum direct wet mounts / stains

Direct/Stains:
• Giemsa/Wright stain of blood, bone marrow, or tissue reveals intracellular yeast cells inside macrophages/monocytes.

• Sabouraud Dextrose Agar (SDA) and Brain Heart Infusion (BHI) with blood.

Histoplasma capsulatum growth media

• Urine/serum Histoplasma antigen assay
• Exoantigen test (H and M bands)
• MALDI-TOF
• PCR.

Histoplasma capsulatum confirmatory tests

Histoplasma capsulatum

Treatments: Itraconazole (mild-to-moderate); liposomal amphotericin B (severe/disseminated).

Eurotiomycetes (Phylum: Ascomycota)

Blastomyces dermatitidis Taxonomic Class & Phylum

Blastomyces dermatitidis

Thermally dimorphic fungus (mold at 25 °C, yeast at 37 °C)

Blastomyces dermatitidis

Macroscopic:
• 25 °C (mold): White-to-tan, flat, woolly-to-glabrous colony.

Blastomyces dermatitidis

Macroscopic:
• 37 °C (yeast): Wrinkled, waxy, cream-to-tan yeast-like colony.

Blastomyces dermatitidis

Microscopic:
• 25 °C (mold): Delicate septate hyphae with single oval or pyriform microconidia borne on short lateral conidiophores ("lollipop" appearance).

Blastomyces dermatitidis

Microscopic:
• 37 °C (yeast): Large (8-15 µm), spherical, broad-based budding yeast with a thick, doubly refractive wall.

Blastomyces dermatitidis

Growth: Slow-to-moderate (1-3 weeks) at 25 °C and 37 °C

Blastomyces dermatitidis

Transmission/Reservoir: Inhalation of conidia; found in moist soil, decaying wood, and organic debris near waterways.

Blastomyces dermatitidis

Risk Factors: Outdoor workers, hunters, campers, dog owners in endemic regions.

Blastomyces dermatitidis direct wet mounts / stains

Direct/Stains:
• 10-20% KOH or tissue section (PAS/GMS) reveals broad-based budding yeast cells.

• SDA and BHI agar.

Blastomyces dermatitidis growth media

• Exoantigen test (A band)
• Chemiluminescent DNA probe
• PCR.

Blastomyces dermatitidis confirmatory tests

Blastomyces dermatitidis

Treatments: Oral itraconazole (mild-to-moderate); amphotericin B (severe/pulmonary/CNS).

Eurotiomycetes (Phylum: Ascomycota)

Coccidioides immitis Taxonomic Class & Phylum

Coccidioides immitis

Thermally dimorphic (mold in environment/culture at 25 °C, spherule in tissue at 37 °C)

Coccidioides immitis

Macroscopic:
• 25 °C (mold): Rapidly growing, white-to-buff, moist colony becoming cottony/powdery with age; extremely hazardous to lab personnel.

Coccidioides immitis

Macroscopic:
• 37 °C (tissue): Forms tissue spherules (does not form yeast on standard culture media).

Coccidioides immitis

Microscopic:
• 25 °C (mold): Branching septate hyphae producing barrel-shaped, thick-walled arthroconidia alternating with clear empty disjunction cells.

Coccidioides immitis

Microscopic:
• 37 °C (tissue): Large, thick-walled spherules (20-80 µm) filled with small endospores (2-5 µm).

Coccidioides immitis

Growth: Rapid growth (3-7 days) at 25 °C. Biosafety Level 3 (BSL-3) pathogen.

Coccidioides immitis

Transmission/Reservoir: Inhalation of airborne arthroconidia from alkaline, desert soil/dust storms.

Coccidioides immitis

Risk Factors: Construction workers, agricultural laborers, residents/travelers in Southwestern US (Arizona, San Joaquin Valley, CA), pregnant women, immunocompromised hosts.

Coccidioides immitis direct wet mounts / stains

Direct/Stains:
• 10-20% KOH or tissue histology (PAS/GMS) reveals spherules containing endospores.

• SDA or Mycosel (handle with extreme caution under BSL-3 safety standards; avoid opening mature plates).

Coccidioides immitis growth media

• Exoantigen test (F and HL bands)
• Tube precipitin/complement fixation serology
• PCR.

Coccidioides immitis confirmatory tests

Coccidioides immitis

Treatments: Fluconazole or itraconazole (pulmonary/meningitis); amphotericin B for severe/disseminated disease.

Eurotiomycetes (Phylum: Ascomycota)

Paracoccidioides brasiliensis Taxonomic Class & Phylum

Paracoccidioides brasiliensis

Thermally dimorphic fungus (mold at 25 °C, yeast at 37 °C)

Paracoccidioides brasiliensis

Macroscopic:
• 25 °C (mold): Slow-growing, flat, white-to-tan velvety colony.

Paracoccidioides brasiliensis

Macroscopic:
• 37 °C (yeast): Cream-colored, wrinkled, yeast-like colony.

Paracoccidioides brasiliensis

Microscopic:
• 25 °C (mold): Mostly sterile, thin septate hyphae with occasional chlamydoconidia and pyriform microconidia.

Paracoccidioides brasiliensis

Microscopic:
• 37 °C (yeast): Large (10-30 µm) central yeast cell surrounded by multiple narrow-based budding yeast cells ("mariner's wheel" / "captain's wheel" appearance).

Paracoccidioides brasiliensis

Growth: Slow growth (2-4 weeks) at 25 and 37 °C

Paracoccidioides brasiliensis

Transmission/Reservoir: Inhalation of fungal spores; soil in humid, subtropical regions.

Paracoccidioides brasiliensis

Risk Factors: Rural agricultural workers (coffee/tobacco farmers) in Latin America; strong male-to-female ratio (~13:1) due to estrogen inhibiting conversion to yeast form.

Paracoccidioides brasiliensis direct wet mounts / stains

Direct/Stains:
• 10-20% KOH of sputum/mucosal scrapings or histology shows "captain's wheel" / "mickey mouse head" yeast morphology.

• SDA and BHI blood agar.

Paracoccidioides brasiliensis growth media

• Immunodiffusion assay (Band 1/Band E)
• Exoantigen test
• PCR.

Paracoccidioides brasiliensis confirmatory tests

Paracoccidioides brasiliensis

Treatments: Itraconazole (first-line); trimethoprim-sulfamethoxazole (cotrimoxazole) for long-term oral therapy; amphotericin B for severe cases.

Eurotiomycetes (Phylum: Ascomycota)

Talaromyces marneffei Taxonomic Class & Phylum

Talaromyces marneffei

Thermally dimorphic fungus (mold at 25 °C, yeast at 37 °C)

Talaromyces marneffei

Macroscopic:
• 25 °C (mold): Rapidly growing, flat, grayish-white colony that produces a soluble diffusible deep red-to-pink pigment into the agar.

Talaromyces marneffei

Macroscopic:
• 37 °C (yeast): Soft, white-to-tan cream-colored yeast-like colony without red pigment.

Talaromyces marneffei

Microscopic:
• 25 °C (mold): Typical Penicillium-like brush structures (biverticillate penicilli with phialides bearing smooth round conidia in chains).

Talaromyces marneffei

Microscopic:
• 37 °C (yeast): Small (2-6 µm), oval yeast cells that divide by binary fission (central septum) rather than budding.

Talaromyces marneffei

Growth: Rapid-to-moderate; distinct thermal dimorphism.

Talaromyces marneffei

Transmission/Reservoir: Inhalation of conidia; soil and exposure to bamboo rats (Rhizomys species).

Talaromyces marneffei

Risk Factors: Immunocompromised individuals, especially HIV/AIDS patients in or traveling to Southeast Asia (Thailand, Vietnam, Southern China).

Talaromyces marneffei direct wet mounts / stains

Direct/Stains:
• Wright/Giemsa stain of skin scrapings or bone marrow shows intracellular/extracellular oval yeast cells with a clear central septum.

• SDA at 25 °C (observing red pigment diffusion) and BHI agar at 37 °C.

Talaromyces marneffei growth media

• Thermal conversion demonstration
• MALDI-TOF MS
• PCR.

Talaromyces marneffei confirmatory tests

Talaromyces marneffei

Treatments: Liposomal amphotericin B initial therapy followed by oral itraconazole maintenance.