Systemic Mycoses: Infections and Pathogens

• Systemic mycoses are fungal infections affecting the entire body or multiple organ systems.
• They are classified as true pathogens (infecting healthy individuals) or opportunistic pathogens (infecting immunocompromised individuals).

Common Systemic Mycoses in the US

• Coccidioidomycosis
• Histoplasmosis
• Paracoccidioidomycosis
• Blastomycosis (in immunocompetent hosts)

Transmission

• A common transmission mode for systemic mycoses is inhaling spores from dimorphic fungi.

Symptoms

• Most lung infections from systemic mycoses are asymptomatic and self-limited.
• In some individuals, the disease progresses, potentially leading to death.

Blastomycosis

• Also known as North American blastomycosis
• Caused by Blastomyces dermatitidis.
• Microconidia produced in the soil become airborne and enter the lungs.
• In the lungs, microconidia germinate into thick-walled yeast cells.
• Yeast cells often appear with unipolar, broad-based buds.
• Primarily found in eastern North America.
• Initial pulmonary infections rarely disseminate, but secondary sites include skin, bone, and the genitourinary tract manifest as ulcerative granulomas.
• Microscopic examination of tissue biopsy specimens reveals thick-walled yeast cells with broad-based buds
• Radiological studies may show diffuse reticular or nodular infiltrates of the lungs.
• Diagnosed via RT-qPCR.

Histoplasmosis

• Caused by Histoplasma capsulatum.
• Histoplasma grows in soil, especially if contaminated with bird droppings.
• Transmitted through inhalation during soil excavation or exploring bat-infested caves.
• Once inhaled, spores convert into yeast-like cells.
• Yeast cells are engulfed and multiplied by macrophages.
• Pulmonary infections are often benign and self-limited, resembling tuberculosis.
• Infections can become chronic and progressive, leading to death.
• Yeast cells within macrophages are seen microscopically in tissue biopsy specimens or bone marrow aspirates.
• Diagnosed by isolating the organism, culturing, or detecting exoantigens in urine.

Coccidioidomycosis

• Caused by Coccidioides immitis
• Common names are Valley Fever and Desert Rheumatism.
• Endemic in arid regions of the southwestern United States and Latin America.
• Dimorphic fungus exists as a mold in soil and as a spherule in tissues.
• In soil, it forms hyphae with alternating arthrospores and empty cells.
• Arthrospores are light and are carried by the wind, infecting the lungs upon inhalation.
• In the lungs, arthrospores form spherules with thick walls filled with endospores.
• When the wall ruptures, endospores are released and differentiate to form new spherules.
• Granulomatous lesions occur primarily in bones and the central nervous system, causing meningitis.
• Infection of the lungs is often asymptomatic.
• Some infected persons develop an influenza-like illness with fever and cough.
• 50% of cases show changes in the lungs, such as infiltrates, adenopathy, or effusions.
• Tissue specimens show spherules stained microscopically.
• Diagnosed via a PCR test.
• Mild or primary infections do not require treatment.
• Persistent lung lesions or disseminated disease are treated with Amphotericin B or itraconazole.
• Fluconazole is the drug of choice for meningitis.

Paracoccidioidomycosis

• Also called South American blastomycosis.
• Caused by Paracoccidioides brasiliensis.
• Clinical presentation is similar to histoplasmosis and blastomycosis.
• The most common secondary site of infection is the mucosa of the mouth and nose, where painful, destructive lesions may develop.
• 90% of symptomatic cases occur in mature males, as estrogen inhibits yeast formation in females, leading to lung lesions.
• Diagnosis is via microscopic view of yeast cells with multiple buds resembling a “ship’s wheel” in tissue specimens (pus or tissues).
• Itraconazole is the treatment of choice.
• Amphotericin B should be used to treat severe disease.
• Surgical excision may be helpful.
• There are no means of prevention.
• Forms granulomas where they spread.
• Forms two types of asexual spores: tuberculated macroconidia and microconidia.
• No therapy is needed for asymptomatic or mild primary infections.
• In disseminated disease, parenteral Itraconazole or Amphotericin B is the treatment of choice.
• Fluconazole is often used as it penetrates the spinal fluid.
• Dissemination is rare but may occur in older adults or individuals with deficiencies in T-cell function, specifically in the liver and spleen
• Histoplasma capsulatum is the only fungus exhibiting intracellular parasitism.
• Disseminated disease results in invasion of cells of the reticuloendothelial system (RES, only intracellular fungus).