Mycology - Systemic Dimorphic Fungi

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Definitive diagnosis of systemic mycoses

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must demonstrate both mold and yeast stages (prove dimorphism) or use molecular methods

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General characteristics

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• Tend to be endemic to a particular geographic region
• Soil, decaying vegetation, bird and bat droppings

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Clinical Significance of systemic mycoses

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• Man is incidental host
• Strict pathogens-able to cause disease in otherwise healthy individuals
• Acquire by inhalation and develop respiratory infection
• Can then become systemic
• Involvement of internal organs including lymph nodes, bone, subcutaneous tissue and skin

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Histoplasmosis

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• Also called spelunker’s disease, Darling’s disease, cave disease
• caused by Histoplasma capsulatum
• Endemic in Mississippi and Ohio River valleys; and Appalachian Mountains
• Found in soil, especially soil contaminated with bat droppings

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Histoplasma capsulatum - Pathogenesis

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• 95% of cases are asymptomatic and self-limiting
• Infection begins in lung and eventually invades the reticuloendothelial system
• Can disseminate to lymphatic tissue, liver, spleen, kidneys, meninges, and heart (esp. in immunocompromised patients)

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Histoplasma capsulatum - direct microscopic examination

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Giemsa or Wright’s stains: Look for small, round to oval yeast cells within mononuclear cells (intracellular)

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Histoplasma capsulatum - mold phase

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• Hyaline, septate hyphae
• Macroconidia are unicellular, hyaline, thick-walled, smooth or warty (tuberculate)
• Microconidia are unicellular, hyaline, with wall smooth or rough
• Can be confused with Sepedonium species (does not have yeast phase)

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Histoplasma capsulatum - yeast phase

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Small budding yeast measuring 2-4 um in length

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Blastomycosis

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• caused Blastomyces dermatitidis
• Endemic in Missouri, Mississippi and Ohio River valleys
• Lives in soil and decaying matter

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Blastomycosis - pathogenesis

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• Majority of infections are asymptomatic and self-limiting
• Infection begins in lung by inhaling conidia or hyphal elements
• Can spread and involve lungs, long bones, soft tissue and skin
• Skin lesions result from bloodborne spread and my become granulomatous and extensive
• Patients with diabetes are at an increased risk of contracting blast

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Blastomycosis - direct examination

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Look for large, spherical, refractile yeast that have a double-contoured wall and buds connected to the parent cell by a broad base

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Blastomyces dermatitidis - mold phase

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Hyaline, septate hyphae

Conidiophores are short, unbranched

Conidia are borne on short lateral branches that are ovoid to dumbbell shaped-resembles “lollipops”

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Blastomyces dermatitidis - yeast phase

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Yeast with refractile walls, budding on a broad base

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Coccidioidomycosis

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• Also called San Joaquin Valley fever, valley fever, desert fever
• Caused by Coccidioides immitis (Endemic in San Joaquin Valley, CA) and Coccidioides posadasii (Endemic in Maricopa and Pima counties of AZ, and southwestern TX)
• Lives in soil

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Coccidioidomycosis pathogenesis

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• 60% of infections are asymptomatic and have self-limited respiratory tract infections
• Infection begins in lung by inhaling arthroconidia (very infectious – 10 conidia inhaled will infect)
• Can disseminate (1%) with extension to visceral organs, meninges, bone, skin, lymph nodes, and subcutaneous tissue

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Coccidioidomycosis - direct examination

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Look for nonbudding spherule, containing either granular material or endospores

• Will not see a yeast form

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Coccidioidomycosis - mold phase

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• Hyaline, septate hyphae
• Conidiophores absent
• Arthroconidia unicellular, rectangular to barrel shaped, often somewhat wider in diameter than the hyphae, alternating with empty cells (disjunctors)

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Coccidioidomycosis - yeast phase

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• Cultivation of spherule phase not recommended
• Use of special media incubated at 40C
• Experimentally infect lab animals and perform tissue biopsy

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Paracoccidiodomycosis

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• Also called South American blastomycosis
• caused by Paracoccidioides brasiliensis
• Central and South America

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Paracoccidiodomycosis - pathogenesis

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• Usually adult males affected because estrogen has an inhibitory effect
• Most infections are asymptomatic
• Pulmonary infection but can disseminate most often resulting in oral and nasal lesions, but can spread to other areas in the body

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Paracoccidiodomycosis - direct examination

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• Look for characteristic yeast cells-Peripheral budding around a large, spherical, double-walled blastoconidium parent cell
• Looks like a ship’s steering wheel or “pilot’s wheel”

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Paracoccidiodomycosis - mold phase

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• Hyaline, septate hyphae with intercalary and terminal chlamydoconidia
• A few microconidia may be observed along the hyphae

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Paracoccidiodomycosis - yeast phase

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• Peripheral budding around a large, spherical, double-walled blastoconidium parent cell
• Looks like a ship’s steering wheel or “pilot’s wheel”

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Systemic Penicilliosis

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Penicillium marneffei

Endemic to southern China and southeast Asia

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Systemic Penicilliosis - pathogenesis

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• Most frequently seen in immunocompromised individuals
• Third most common cause of disseminated opportunistic infection in AIDS patients in endemic areas
• Cutaneous lesions are frequently present
• Disseminated disease is typically fatal

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Systemic Penicilliosis - direct examination

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Small, oval yeast-like cells within the cytoplasm of phagocytes and may resemble Histoplasma capsulatum

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Systemic Penicilliosis - mold phase

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Hyaline, septate hyphae with smooth conidiophores with 4-5 metulae that support 4-6 phialides with chains of smooth or slightly rough conidia

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Systemic Penicilliosis - yeast phase

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Yeast-like forms develop with internal cross-walls present and no budding • 2-6 um