Fungal Diseases

March 24th, 2010

Fungi fundamentals

• Occupy almost every ecological niche• Exist in two forms:• Yeasts

– Single celled

• Molds– Growth in branching chains called hyphae

• Dimorphic– Have both yeast and mold life stages

Fungi fundamentals

• Life stages• Mold in soil• Yeast in tissues• Mold phase produces spores that

spread the organism in the environment and also cause infection

Diagnosis and Identification

• PCR• Use of immunological techniques to

identify antibodies to infection in people

• Microscopy and culture• Identification by visual examination

of appearance

Candida

Candida

Candida (wet mount)

Fungal pathogenesis

• Some fungi produce mycotoxins• Grow in tissue, spread through organs• Superficial infections• 1Skin• Systemic infections (disseminated)

– Most severe kind– Immunosuppressed people are at high

risk

Coccidioidomycosis

• Valley fever• Agent: Coccidioides immitis• Reservoir: soil• Arid climates• Endemic to southwestern US

– Arizona and California

• S. America– Brazil, Colombia, Mexico, Venezuela

Coccidioidomycosis

• Infection is by inhalation of arthroconidia• Arthroconidia

– Spores that form from segments of the hyphae

• Become airborne when dust is disturbed• Inhaled, infection begins in the lungs• Once in tissues, fungus forms spherules

(spherical cells) and reproduces

Arthroconidia

Life cycle of valley fever

Disease process

• Initial infection via the lungs• May be asymptomatic

– Probably very common in endemic areas

• May cause flulike symptoms• For many people with healthy immune

systems, infection is self-limiting• Confers long-term immunity• May leave calcified lesions in the lungs

Disseminated infection

• About 1% of symptomatic infections become disseminated

• Most dangerous type of infection• Fatal without treatment• Growth in body tissues

– Skin– Bone – Meninges

• More common in immunosuppression

Clinical valley fever

Diagnosis

• Visualization of spherules under the microscope

• Culture of fungi from tissue samples in the laboratory

• Handling of the spores is high-risk; laboratory acquired infection is an occupational hazard for people who work with valley fever

Treatment

• Antifungal drugs• Amphotericin B

– Produced by bacteria (Streptomyces)– Effective, but quite toxic– Kidney damage– IV administration

• Newer drugs: Azoles– fluconazole

Cryptococcus neoformans

Cryptococcus

• Cryptococcal meningitis• Agent: Cryptococcus neoformans• Reservoir: soil• Infection by inhalation• Primary site of infection is the lungs• Can disseminate from there

Cryptococcus

Cryptococcus

• Humans are fairly resistant• Severe infection is seen in

immunocompromised individuals• Opportunistic infection of AIDS• Cases have tended to follow the

pattern of AIDS epidemics in a given area

Cryptococcus

• Diagnosis by visualization in CSF• Confirmation by culture or

observation of growth in histological samples

• Treatment• Amphotericin B + 5-flucytosine• Maintenance therapy with

fluconazole

Histoplasmosis

• Agent: Histoplasma capsulatum• Reservoir: soil• Soil contaminated by birds is high risk• Primary infection is in the lungs• Different disease courses

– Self-limiting– Systemic – Chronic pulmonary

Histoplasmosis