This document provides an overview of medical mycology, including: 1. It classifies fungi and discusses their morphology, including yeasts, hyphae, and dimorphic fungi. 2. It covers the epidemiology of fungal infections, including endemic mycoses caused by dimorphic fungi. 3. It discusses the diagnosis of fungal infections through wet mounts, skin tests, serology, biopsy, and culture. 4. It outlines the treatment of fungal infections through antifungal agents like polyenes, azoles, and others.

1. Medical Mycology Outline Introduction, Actinomycetes Yeasts, Dermatophytes Filamentous Fungi, Dimorphic Fungi Dimorphic Fungi Opportunistic Fungi www.freelivedoctor.com

2. INTRODUCTION www.freelivedoctor.com

3. A. Classification www.freelivedoctor.com

4. What is a Fungus ? Eukaryotic – a true nucleus Do not contain chlorophyll Have cell walls Produce filamentous structures Produce spores www.freelivedoctor.com

5. Species of Fungi 100,000 – 200,000 species About 300 pathogenic for man www.freelivedoctor.com

6. Kingdom Fungi Eukaryocytes Ascomycota Basidiomycota Zygomycota Mitosporic Fungi (Fungi Imperfecti) www.freelivedoctor.com

7. www.freelivedoctor.com KINGDOM CHARACTERISTIC EXAMPLE Monera Prokaryocyte Bacteria Actinomyces Protista Eukaryocyte Protozoa Fungi Eukaryocyte * Fungi Plants Eukaryocyte Plants Moss Animals Eukaryocyte * Arthropods Mammals Man

8. www.freelivedoctor.com KINGDOM CHARACTERISTIC EXAMPLE Monera Prokaryocyte Bacteria Actinomyces Protista Eukaryocyte Protozoa Fungi Eukaryocyte * Fungi Plants Eukaryocyte Plants Moss Animals Eukaryocyte * Arthropods Mammals Man

9. SIZE COMPARISON OF PATHOGENS www.freelivedoctor.com Cocci 0.8 u Bacilli 4-6 u Spirochetes 8 - 10 u Viruses 0.08 u Protozoa 15 u Nematodes 10 mm Fungi 10 – 15 u

10. Actinomyces (True Bacteria) Tradition Clinical infection resembles mycoses Actinomyces grow on mycotic media Actinomyces grow slowly (24-48 h) Gross colonies resemble fungi (rough,heaped, short aerial filaments) Resemble mycelia microscopically, with branched mycelia in tissue and smears. www.freelivedoctor.com

11. MYCOTIC DISEASES (Four Types) Hypersensitivity Allergy Mycotoxicosis Production of toxin Mycetismus (mushroom poisoning) Pre-formed toxin Infection www.freelivedoctor.com

12. Hypersensitivity FARMER’S LUNG – Moldy hay MALT WORKER’S DISEASE – Moldy barley CHEESE WASHER’S LUNG – Moldy cheese WOOD TRIMMER’S DISEASE – Moldy wood www.freelivedoctor.com

13. PATHOGENIC FUNGI NORMAL HOST Systemic pathogens - 25 species Cutaneous pathogens - 33 species Subcutaneous pathogens - 10 species IMMUNOCOMPROMISED HOST Opportunistic fungi - 300 species www.freelivedoctor.com

14. PARASITIC STATE Increased metabolic state Modified metabolic pathways Modified cell wall structure Carbohydrate content Lipid structure RNA aggregates www.freelivedoctor.com

15. PATHOGENICITY OF FUNGI Thermotolerance Ability to survive in tissue environment Ability to withstand host defenses www.freelivedoctor.com

16. REVIVED INTEREST IN MYCOLOGY Increased frequency of mycotic diseases Increased awareness by physicians Better trained laboratory personnel More invasive procedures used on patients Increased use of immunosuppressive drugs Increase in immunosuppressive disease 7. Better laboratory diagnostic tools www.freelivedoctor.com

17. B. MORPHOLOGY www.freelivedoctor.com

18. MORPHOLGY Yeasts Hyphae (filamentous fungi, mycelium) Septate Coenocytic (non-septate) Dimorphic Yeast Mycelium www.freelivedoctor.com

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22. Dimorphic Fungi Yeast Form Parasitic form Tissue form Cultured at 37 C Mycelial Form Saprophytic form Cultured at 25 C www.freelivedoctor.com

23. SPORES SEXUAL ASEXUAL Arthrospore Blastospore Chamydospore Conidia Microconidia Macroconidia www.freelivedoctor.com

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27. C. EPIDEMIOLOGY www.freelivedoctor.com

28. ECOLOGICAL ASSOCIATION PATHOGEN HUMAN SOIL _________________________________________ Blastomyces dermatitidis 1898 1964 Cryptococcus neoformans 1894 1951 Coccidioides immitis 1900 1932 Histoplasma capsulatum 1934 1949 www.freelivedoctor.com

29. Mycotic Diseases Are NOT Contagious www.freelivedoctor.com

30. ESTABLISHMENT OF INFECTION WITH A MYCOTIC AGENT DEPENDS ON Inoculum size Resistance of the host www.freelivedoctor.com

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32. THE CLINICIAN MUST DISTINGUISH BETWEEN: COLONIZATION FUNGEMIA INFECTION www.freelivedoctor.com

33. PORTAL OF ENTRY EYE SKIN UROGENITAL TRACT ANUS MOUTH RESPIRATORY TRACT SKIN HAIR NAILS RESPIRATORY TRACT GASTROINTESTINAL TRACT URINARY TRACT www.freelivedoctor.com

34. COLONIZATION EYE SKIN UROGENITAL TRACT ANUS MOUTH RESPIRATORY TRACT Multiplication of an organism at a given site without harm to the host www.freelivedoctor.com

35. INFECTION EYE SKIN UROGENITAL TRACT ANUS MOUTH RESPIRATORY TRACT Invasion and multiplication of organisms in body tissue resulting in local cellular injury . www.freelivedoctor.com

36. GEOGRAPHIC DISTRIBUTION The present ease and frequency of world-wide travel make it more likely that physicians in the United States will be confronted with a variety of unfamiliar mycoses acquired in distant parts of the country or of the world. www.freelivedoctor.com

37. Endemic Mycoses Those fungus infections with a limited geographic distribution. They are all caused by dimorphic fungi www.freelivedoctor.com

38. D. DIAGNOSIS www.freelivedoctor.com

39. Diagnosis 1. Wet Mount 2. Skin test 3. Serology 4. Fluorescent antibody 5. Biopsy and histopathology 6. Culture 7. DNA probes www.freelivedoctor.com

40. Diagnosis 1. Wet Mount 2. Skin test 3. Serology 4. Fluorescent antibody 5. Biopsy and histopathology 6. Culture 7. DNA probes www.freelivedoctor.com

41. DIRECT MICROSCOPIC OBSERVATION 10 % KOH Gentle Heat www.freelivedoctor.com

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43. KOH Wet Mount www.freelivedoctor.com

44. Diagnosis 1. Wet Mount 2. Skin test 3. Serology 4. Fluorescent antibody 5. Biopsy and histopathology 6. Culture 7. DNA probes www.freelivedoctor.com

45. SKIN TESTING (DERMAL HYPERSENSTIVITY ) Use is limited to : Determine cellular defense mechanisms Epidemiologic studies www.freelivedoctor.com

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47. Diagnosis 1. Wet Mount 2. Skin test 3. Serology 4. Fluorescent antibody 5. Biopsy and histopathology 6. Culture 7. DNA probes www.freelivedoctor.com

48. FUNGI ARE POOR ANTIGENS www.freelivedoctor.com

49. FUNGAL SEROLOGY ANTIBODIES Latex Agglutination IgM Immunodiffusion IgG Complement Fixation IgG www.freelivedoctor.com

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51. DIRECT FLUORESCENT ANTIBODY CAN BE APPLIED TO HISTOLOGIC SECTIONS CULTURE Viable organisms Non-viable organisms www.freelivedoctor.com

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53. INCUBATION TEMPERATURE 37 C - Body temperature 25 C - Room temperature www.freelivedoctor.com

54. E. TREATMENT www.freelivedoctor.com

55. THERAPY Because they are eukaryotic, fungi are biochemically similar to the human host. Therefore it is difficult to develop chemotherapeutic agents that will destroy the invading fungus without harming the patient. www.freelivedoctor.com

56. A BASIC TENET OF PATHOLGY : A CAUSE OF IRREVERSIBLE CELL INJURY IS CELL MEMBRANE DAMAGE. www.freelivedoctor.com

57. IN FUNGAL THERAPY We attempt to induce cell injury by causing the cell membrane of the fungus to become permeable. www.freelivedoctor.com

58. PRIMARY ANTI-FUNGAL AGENTS Polyene derivatives Amphotericin B Nystatin Azoles Ketoconazole Fluconazole Itraconazole Voriconazole Posaconazole www.freelivedoctor.com

59. AMPHOTERICIN B Mechanism of Action Amphotericin B binds to sterols Ergosterol is a constituent of the fungal cell wall AMB has a greater avidity for ergosterol than for the cholesterol in the human cell wall Binding to the fungal cell wall alters the permeability and the intracellular contents leak www.freelivedoctor.com

60. AMPHOTERICIN B Disadvantages Intravenous administration Thrombophlebitis Nephrotoxic Fever Chills Anemia Long term administration www.freelivedoctor.com

61. Azoles There are a few rare serious side effects from Itraconazole and Fluconazole www.freelivedoctor.com

62. PRIMARY ANTI-FUNGAL AGENTS 3. Griseofulvin 4. 5-fluorocytosine (5-FC) 5. Allylamines -Terbinafine (Lamasil) 6. Echinocandins - Caspofungin www.freelivedoctor.com

63. Griseofulvin A slow acting drug used for skin and nail infections. It accumulates in the stratum corneum and prevent hyphal penetration through these layers www.freelivedoctor.com

64. 5- fluorocytosine (5-FC) Interferes With RNA Synthesis www.freelivedoctor.com

65. MECHANISMS OF ACTION Polyenes Azoles Griseofulvin 5 - FC Ergosterol in cell membrane Interfere with ergosterol synthesis Forms a barrier to fungal growth Inhibits RNA synthesis www.freelivedoctor.com

66. F. Clinical Classification of Mycoses Cutaneous Subcutaneous Systemic Opportunistic www.freelivedoctor.com

67. Cutaneous Mycoses Skin, hair and nails Rarely invade deeper tissue Dermatophytes www.freelivedoctor.com

68. Subcutaneous Mycoses Confined to subcutaneous tissue and rarely spread systemically. The causative agents are soil organisms introduced into the extremities by trauma www.freelivedoctor.com

69. Systemic Mycoses Involve skin and deep viscera May become widely disseminated Predilection for specific organs www.freelivedoctor.com