1. C H A P T E R © 2014 Pearson Education, Inc. PowerPoint ® Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University 22 Pathogenic Fungi

2. © 2014 Pearson Education, Inc. An Overview of Medical Mycology Medical mycology Diagnosis, management, and prevention of fungal diseases (mycoses) Mycoses are among the most difficult diseases to diagnose and treat Signs of mycoses are often missed or misinterpreted Fungi are often resistant to antifungal agents

3. © 2014 Pearson Education, Inc. An Overview of Medical Mycology The Epidemiology of Mycoses Fungi and their spores are almost everywhere in the environment Most people will experience a mycosis at some time Typically acquired via inhalation, trauma, or ingestion Infrequently spread from person to person Most mycoses are not contagious Dermatophytes are the major exception Epidemics due to mass exposure to environmental source of fungi Mycoses are generally not reportable Adequate information on their occurrence is often lacking

4. © 2014 Pearson Education, Inc. An Overview of Medical Mycology Categories of Fungal Agents: True Fungal Pathogens and Opportunistic Fungi Only four fungi usually considered true pathogens Other fungi are opportunistic Certain factors increase risk for opportunistic mycoses Invasive medical procedure Medical therapies Certain disease conditions Specific lifestyle factors True pathogens endemic primarily in the Americas Opportunists distributed throughout the world

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6. An Overview of Medical Mycology Clinical Manifestations of Fungal Diseases Three categories of clinical manifestation Fungal infections Most common mycoses Caused by presence of true pathogens or opportunists Toxicoses Acquired through ingestion Occur when poisonous mushrooms are eaten Allergies Most often result from the inhalation of fungal spores

7. © 2014 Pearson Education, Inc. An Overview of Medical Mycology Antifungal Therapies Mycoses are among the most difficult diseases to heal Fungi often resist T cell–mediated immune responses Fungi biochemically similar to human cells Antifungal drugs can harm human tissues Ergosterol is often a target of antifungal drugs Amphotericin B is gold standard of antifungals One of the more toxic antifungal agents Less toxic alternatives include ketoconazole, itraconazole, and fluconazole

8. © 2014 Pearson Education, Inc. An Overview of Medical Mycology Antifungal Vaccines Antifungal vaccines have been difficult to develop Fungal metabolism similar to our own Scientists have developed vaccines against some fungi Coccidioides Blastomycosis Candida

9. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Pathogenic Fungi Systemic mycoses Infections spread throughout the body Caused by four pathogenic fungi of the division Ascomycota Blastomyces Coccidioides Histoplasma Paracoccidioides Acquired through inhalation Begins as generalized pulmonary infection Disseminates via the blood to the rest of the body

10. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Pathogenic Fungi Systemic mycoses All four fungi are dimorphic Grow as mycelial thalli in the environment Grow as spherical yeasts in the body Invasive form Individuals working with these fungi must take precautions to avoid exposure to spores

11. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Pathogenic Fungi Histoplasmosis Histoplasma capsulatum is the causative agent Most common fungal pathogen affecting humans Found in the eastern United States, Africa, and South America Fungi found in moist soils containing high nitrogen levels Most infections occur through inhalation of spores Cutaneous inoculations are extremely rare H. capsulatum is phagocytized by macrophages in the lungs Disperse the fungi beyond the lungs via the blood and lymph

12. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Pathogenic Fungi Histoplasmosis Usually asymptomatic and resolves without damage Clinical histoplasmosis results in one of four diseases Chronic pulmonary histoplasmosis Chronic cutaneous histoplasmosis Systemic histoplasmosis Ocular histoplasmosis Diagnosis based on identification of yeast in patient sample Infections in healthy individuals resolve on their own Treated with amphotericin B or ketoconazole when needed

13. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Pathogenic Fungi Blastomycosis Blastomyces dermatitidis is the causative agent Endemic in the southeastern United States north to Canada Fungi found in soils rich in organic matter Pulmonary blastomycosis Most common manifestation Initial pulmonary lesions are mostly asymptomatic When symptoms occur they are nonspecific The disease resolves in most people but may become chronic

14. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Pathogenic Fungi Blastomycosis Cutaneous blastomycosis Painless lesions on the face and upper body Osteoarticular blastomycosis Spread of the fungus to the spine, pelvis, cranium, ribs, long bones, or subcutaneous tissues surrounding joints Meningitis Dissemination of the fungus to the central nervous system Can occur in AIDS patients Diagnosis based on identification of fungi in culture or samples Treat with amphotericin B or oral itraconazole Relapse is common in AIDS patients

15. © 2014 Pearson Education, Inc. Figure 22.6 Cutaneous blastomycosis in an American woman.

16. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Pathogenic Fungi Coccidioidomycosis Coccidioides immitis is the causative agent Almost exclusively in the southwestern United States and northern Mexico Fungi in desert soil, rodent burrows, archeological remains, mines Infection rates have risen in endemic areas Population expansion and increased recreational activities Inhaled arthroconidia germinate into spherules in the lung Spherules release large number of spores as they mature

17. © 2014 Pearson Education, Inc. SpheruleSpores Figure 22.8 Spherules of Coccidioides immitis.

18. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Pathogenic Fungi Coccidioidomycosis Coccidioidomycoses most often result in pulmonary conditions Many patients show no or few symptoms Infections in healthy individuals resolve on their own Some individuals develop more serious infections Dissemination to other sites occurs mostly in immunocompromised Diagnosis based on presence of spherules in patient samples or a positive coccidioidin skin test Amphotericin B is the drug of choice for treatment Maintenance therapy can help prevent relapse in AIDS patients Wearing protective masks in endemic areas can prevent exposure to spores

19. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Pathogenic Fungi Paracoccidioidomycosis Paracoccidioides brasiliensis is the causative agent Found in southern Mexico and regions of South America Disease found mostly in farm workers in endemic areas Similar to blastomycosis and coccidioidomycosis Infection begins as a pulmonary condition The fungus almost always spreads Produces chronic inflammatory disease of mucous membranes Diagnosis based on the presence of yeast in a "steering wheel" formation in patient samples Treatment is with amphotericin B or ketoconazole

20. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Opportunistic Fungi Opportunistic mycoses don't typically affect healthy humans Infections limited to people with poor immunity More important as the number of AIDS patients rises Difficult to identify because their symptoms are often atypical

21. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Opportunistic Fungi Pneumocystis Pneumonia Pneumocystis jiroveci is causative agent Formerly referred to as P. carinii Obligate parasite Majority of individuals exposed to P. jiroveci by age five Transmission most likely occurs through inhalation Infection in immunocompetent is usually asymptomatic Common opportunistic fungal infection of AIDS patients Presence of the disease is almost diagnostic for AIDS Can result in death if left untreated Diagnosed based on clinical and microscopic findings Treatment is with trimethoprim and sulfanilamide

22. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Opportunistic Fungi Candidiasis Includes various opportunistic infections and diseases Candida albicans is the most common causative agent Common microbiota of the skin and mucous membranes Candida is one of the few fungi transmitted between individuals All cases of disease result from an opportunistic infection Can produce a wide range of diseases Systemic disease seen mostly in immunocompromised individuals

23. © 2014 Pearson Education, Inc. Figure 22.12 Three of the many manifestations of candidiasis.

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25. Systemic Mycoses Caused by Opportunistic Fungi Candidiasis Diagnosis based on presence of clusters of budding yeasts and pseudohyphae Treatment depends on the particular disease Treat underlying problem in immunocompetent individuals Oral candidiasis in infants treated with nystatin Vaginal candidiasis treated with azole suppositories, creams, or oral fluconazole Infections in AIDS patients difficult to treat Oral fluconazole used for primary and maintenance therapy Amphotericin B or 5-fluorocytosine used for invasive candidiasis

26. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Opportunistic Fungi Aspergillosis Several diseases caused by fungi in the genus Aspergillus Can be found throughout the environment Disease occurs from the inhalation of the fungal spores Most commonly causes only allergies

27. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Opportunistic Fungi Aspergillosis Three pulmonary diseases may develop Hypersensitivity aspergillosis Manifests as asthma or other allergic symptoms Noninvasive aspergillomas Masses of fungal hyphae form in the cavities following pulmonary tuberculosis Acute invasive pulmonary aspergillosis May present as pneumonia Cutaneous and systemic aspergillosis also occur

28. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Opportunistic Fungi Aspergillosis Presence of septate hyphae and distinctive conidia in patient samples is diagnostic Detection of antigens in the blood is confirmatory Hypersensitivity aspergillosis treated with allergy medications Invasive disease treated by surgical removal of aspergillomas and intravenous amphotericin B Systemic infections treated with amphotericin B along with other antifungal agents Itraconazole is used as maintenance therapy for AIDS patients

29. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Opportunistic Fungi Cryptococcosis Cryptococcus neoformans is the main causative agent Two varieties Cryptococcus neoformans gattii Infects immunocompetent individuals Cryptococcus neoformans neoformans Infects AIDS patients Results from inhalation of spores or dried yeast in bird droppings Characteristics enhance the pathogenicity of the fungus Ability to resist phagocytosis Predilection for the central nervous system Occurs in individuals with little immune system function

30. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Opportunistic Fungi Cryptococcosis Various diseases can result from infection Primary pulmonary cryptococcus Asymptomatic or mild pneumonia Cryptococcal meningitis Most common clinical form of cryptococcal infection Follows dissemination of the fungus to the CNS Cryptococcoma Rare condition in which solid fungal masses can form Cutaneous cryptococcosis Skin lesions or inflammation of subcutaneous tissues

31. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Opportunistic Fungi Zygomycoses Infections caused by genera in the division Zygomycota Common in the environment with worldwide distribution Seen in several groups Individuals with uncontrolled diabetes People who inject illegal drugs Some cancer patients Some patients receiving antimicrobial drugs Infections usually develop in the face and head area

32. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Opportunistic Fungi Zygomycoses Can spread and cause various conditions Rhinocerebral zygomycosis Infection of the paranasal sinuses that can invade the brain Pulmonary zygomycosis Cavities form in the lungs following inhalation of spores Gastrointestinal zygomycosis Involves ulcers in the intestinal tract Cutaneous zygomycosis Introduction of fungi through the skin after trauma

33. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Opportunistic Fungi The Emergence of Fungal Opportunists in AIDS Patients AIDS patients vulnerable to opportunistic fungal infections Permanent immune dysfunction makes cure of infections unlikely Mycoses account for most deaths associated with AIDS Infection with various fungi partly define end-stage AIDS Emergence of new fungal opportunists Increase in immunocompromised individuals Use of antifungal drugs selects for fungi resistant to the drugs

34. © 2014 Pearson Education, Inc. Systemic Mycoses Caused by Opportunistic Fungi The Emergence of Fungal Opportunists in AIDS Patients Three emerging pathogens are particularly problematic Fusarium species Cause respiratory distress, disseminated infections, and fungemia Toxin accumulation can occur when fungi ingested in food Penicillium marneffei Produces pulmonary disease if inhaled Trichosporon beigelii Can cause fatal systemic disease in AIDS patients Enters through the lungs, gastrointestinal tract, or catheters

35. © 2014 Pearson Education, Inc. Superficial, Cutaneous, and Subcutaneous Mycoses Superficial Mycoses Are the most common fungal infections Confined to the outer, dead layers of the skin, nails, or hair All composed of dead cells that contain keratin Primary food of these fungi

36. © 2014 Pearson Education, Inc. Superficial, Cutaneous, and Subcutaneous Mycoses Superficial Mycoses Dermatophytoses Infections of the skin, nails, or hair caused by dermatophytes Previously called ringworms Fungi use keratin as nutrient source and colonize dead tissues May trigger cell-mediated immune response that damages living tissues Can be spread from person to person Genera of ascomycetes cause most dermatophytoses Dermatophytoses show a variety of clinical manifestations

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38. Superficial, Cutaneous, and Subcutaneous Mycoses Superficial Mycoses Dermatophytoses Most dermatophytoses are clinically distinctive Confirm by identification of hyphae or arthroconidia in patient samples Treat limited infections with topical antifungal agents Treat widespread infections with oral antifungal agents Terbinafine is usually effective Griseofulvin is used for chronic or difficult cases

39. © 2014 Pearson Education, Inc. Superficial, Cutaneous, and Subcutaneous Mycoses Superficial Mycoses Malassezia infections Caused by Malassezia furfur Normal microbiota of the skin Causes pityriasis Depigmented or hyperpigmented patches of scaly skin Diagnosis based on presence of budding yeast and short hyphal forms in clinical samples Superficial infections are treated with topical antifungal agents Extensive infections are treated with oral therapy Relapses of Malassezia infections are common

40. © 2014 Pearson Education, Inc. Figure 22.16 Pityriasis.

41. © 2014 Pearson Education, Inc. Superficial, Cutaneous, and Subcutaneous Mycoses Cutaneous and Subcutaneous Mycoses Fungi are commonly found in the soil Less common than superficial mycoses Requires traumatic introduction of fungi beneath the outer layers of skin Most lesions remain localized to subepidermal tissues in the skin

42. © 2014 Pearson Education, Inc. Superficial, Cutaneous, and Subcutaneous Mycoses Cutaneous and Subcutaneous Mycoses Chromoblastomycosis and phaeohyphomycosis Similar cutaneous and subcutaneous mycoses Caused by dark-pigmented ascomycetes Incidence of infection is relatively low Individuals who work in the soil are most at risk

43. © 2014 Pearson Education, Inc. Superficial, Cutaneous, and Subcutaneous Mycoses Cutaneous and Subcutaneous Mycoses Chromoblastomycosis and phaeohyphomycosis Chromoblastomycosis Produces lesions on skin surface that progressively worsen Phaeohyphomycosis Involves colonization of the nasal passages and sinuses Occurs in allergy sufferers and AIDS patients Distinguish the two diseases based on the morphology of fungal cells in tissue samples Both diseases are difficult to treat

44. © 2014 Pearson Education, Inc. Figure 22.17 A leg with extensive lesions of chromoblastomycosis.

45. © 2014 Pearson Education, Inc. Superficial, Cutaneous, and Subcutaneous Mycoses Cutaneous and Subcutaneous Mycoses Mycetomas Tumorlike infections Caused by mycelial fungi in the division Ascomycota Infections are most prevalent near the equator Fungi are found in the soil Fungi introduced via wounds from contaminated twigs, thorns, or leaves Individuals who work in the soil are most at risk Nodules form at site of infection and slowly worsen and spread Bone destruction can cause permanent deformity

46. © 2014 Pearson Education, Inc. Figure 22.19 A mycetoma of the ankle.

47. © 2014 Pearson Education, Inc. Superficial, Cutaneous, and Subcutaneous Mycoses Cutaneous and Subcutaneous Mycoses Mycetomas Diagnosis based on symptoms and presence of fungi in patient samples Surgical removal of the mycetoma is required for treatment Surgery followed by one to three years of therapy with ketoconazole

48. © 2014 Pearson Education, Inc. Superficial, Cutaneous, and Subcutaneous Mycoses Cutaneous and Subcutaneous Mycoses Sporotrichosis Sporothrix schenckii is the causative agent Subcutaneous infection usually limited to the arms and legs Fungi found in the soil Those who work with plant material at highest risk for infection Most infections occur in Latin America, Mexico, and Africa

49. © 2014 Pearson Education, Inc. Fungal Intoxications and Allergies Some fungi produce mycotoxins or cause allergies Fungal mycotoxins can cause toxicosis Two types of toxicosis Mycotoxicosis Caused by eating mycotoxins Mycetismus Mushroom poisoning from eating a fungus Fungal allergens can elicit hypersensitivity response in sensitive individuals

50. © 2014 Pearson Education, Inc. Fungal Intoxications and Allergies Mycotoxicoses Mycotoxins Produced by fungi during normal metabolic activities Often consumed in grains or vegetables Aflatoxins are the best-known mycotoxins Fatal to many vertebrates Carcinogenic at low levels when consumed continually Can cause liver damage and liver cancer Prevalent in the tropics Some mycotoxins are used to make drugs Include ergot alkaloids produced by Claviceps purpurea

51. © 2014 Pearson Education, Inc. Fungal Intoxications and Allergies Mushroom Poisoning (Mycetismus) Most mushrooms are not toxic Some produce extremely dangerous poisons Can cause neurological dysfunction, hallucinations, organ damage, or death Poisoning typically occurs when untrained individuals pick and eat wild mushrooms Deadliest mushroom toxins produced by the "death cap" mushroom Damage cell structure and inhibit mRNA synthesis Cause liver damage

52. © 2014 Pearson Education, Inc. Figure 22.21 Amanitaphalloides, the "death cap” mushroom.

53. © 2014 Pearson Education, Inc. Fungal Intoxications and Allergies Mushroom Poisoning (Mycetismus) Other deadly mushrooms Gyromitra esculenta causes diarrhea, convulsions, and death Cortinarius gentilis causes thirst, nausea, and kidney failure Some mushrooms produce hallucinogenic toxins Psilocybe cubensis produces psilocybin Amanita muscaria produces ibotenic acid and muscimol Treatment involves induced vomiting and administration of activated charcoal to absorb toxins A liver transplant may be needed in cases of severe poisoning

54. © 2014 Pearson Education, Inc. Fungal Intoxications and Allergies Allergies to Fungi Fungal allergens are common both indoors and out Determining specific cause can be difficult Due to presence of fungi in the environment Fungal allergens usually cause type I hypersensitivity Result in asthma, eczema, and hay fever Type III hypersensitivity reactions occur much less frequently