1. Fungal Diseases March 24 th, 2010

2. 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

3. 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

4. Diagnosis and Identification PCR Use of immunological techniques to identify antibodies to infection in people Microscopy and culture Identification by visual examination of appearance

5. Candida

7. Candida (wet mount)

8. 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

9. Coccidioidomycosis Valley fever Agent: Coccidioides immitis Reservoir: soil Arid climates Endemic to southwestern US –Arizona and California S. America –Brazil, Colombia, Mexico, Venezuela

10. 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

11. Arthroconidia

12. Life cycle of valley fever

13. 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

14. 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

15. Clinical valley fever

16. 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

17. Treatment Antifungal drugs Amphotericin B –Produced by bacteria (Streptomyces) –Effective, but quite toxic –Kidney damage –IV administration Newer drugs: Azoles –fluconazole

18. Cryptococcus neoformans

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

20. Cryptococcus

21. 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

22. 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

23. 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

24. Histoplasmosis