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Introduction

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  • 1. Medical Mycology Outline <ul><li>Introduction, Actinomycetes </li></ul><ul><li>Yeasts, Dermatophytes </li></ul><ul><li>Filamentous Fungi, Dimorphic Fungi </li></ul><ul><li>Dimorphic Fungi </li></ul><ul><li>Opportunistic Fungi </li></ul>www.freelivedoctor.com
  • 2. INTRODUCTION www.freelivedoctor.com
  • 3. A. Classification www.freelivedoctor.com
  • 4. What is a Fungus ? <ul><li>Eukaryotic – a true nucleus </li></ul><ul><li>Do not contain chlorophyll </li></ul><ul><li>Have cell walls </li></ul><ul><li>Produce filamentous structures </li></ul><ul><li>Produce spores </li></ul>www.freelivedoctor.com
  • 5. Species of Fungi <ul><li>100,000 – 200,000 species </li></ul><ul><li>About 300 pathogenic for man </li></ul>www.freelivedoctor.com
  • 6. Kingdom Fungi Eukaryocytes <ul><li>Ascomycota </li></ul><ul><li>Basidiomycota </li></ul><ul><li>Zygomycota </li></ul><ul><li>Mitosporic Fungi </li></ul><ul><li>(Fungi Imperfecti) </li></ul>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) <ul><li>Tradition </li></ul><ul><li>Clinical infection resembles mycoses </li></ul><ul><li>Actinomyces grow on mycotic media </li></ul><ul><li>Actinomyces grow slowly (24-48 h) </li></ul><ul><li>Gross colonies resemble fungi </li></ul><ul><ul><li>(rough,heaped, short aerial filaments) </li></ul></ul><ul><li>Resemble mycelia microscopically, with branched mycelia in tissue and smears. </li></ul>www.freelivedoctor.com
  • 11. MYCOTIC DISEASES (Four Types) <ul><li>Hypersensitivity </li></ul><ul><ul><li>Allergy </li></ul></ul><ul><li>Mycotoxicosis </li></ul><ul><ul><li>Production of toxin </li></ul></ul><ul><li>Mycetismus (mushroom poisoning) </li></ul><ul><ul><li>Pre-formed toxin </li></ul></ul><ul><li>Infection </li></ul>www.freelivedoctor.com
  • 12. Hypersensitivity <ul><li>FARMER’S LUNG – Moldy hay </li></ul><ul><li>MALT WORKER’S DISEASE – Moldy barley </li></ul><ul><li>CHEESE WASHER’S LUNG – Moldy cheese </li></ul><ul><li>WOOD TRIMMER’S DISEASE – Moldy wood </li></ul>www.freelivedoctor.com
  • 13. PATHOGENIC FUNGI <ul><li>NORMAL HOST </li></ul><ul><ul><li>Systemic pathogens - 25 species </li></ul></ul><ul><ul><li>Cutaneous pathogens - 33 species </li></ul></ul><ul><ul><li>Subcutaneous pathogens - 10 species </li></ul></ul><ul><li>IMMUNOCOMPROMISED HOST </li></ul><ul><ul><ul><li>Opportunistic fungi - 300 species </li></ul></ul></ul>www.freelivedoctor.com
  • 14. PARASITIC STATE <ul><li>Increased metabolic state </li></ul><ul><li>Modified metabolic pathways </li></ul><ul><li>Modified cell wall structure </li></ul><ul><ul><li>Carbohydrate content </li></ul></ul><ul><ul><li>Lipid structure </li></ul></ul><ul><ul><li>RNA aggregates </li></ul></ul>www.freelivedoctor.com
  • 15. PATHOGENICITY OF FUNGI <ul><li>Thermotolerance </li></ul><ul><li>Ability to survive in tissue environment </li></ul><ul><li>Ability to withstand host defenses </li></ul>www.freelivedoctor.com
  • 16. REVIVED INTEREST IN MYCOLOGY <ul><li>Increased frequency of mycotic diseases </li></ul><ul><li>Increased awareness by physicians </li></ul><ul><li>Better trained laboratory personnel </li></ul><ul><li>More invasive procedures used on patients </li></ul><ul><li>Increased use of immunosuppressive drugs </li></ul><ul><li>Increase in immunosuppressive disease </li></ul><ul><li>7. Better laboratory diagnostic tools </li></ul>www.freelivedoctor.com
  • 17. B. MORPHOLOGY www.freelivedoctor.com
  • 18. MORPHOLGY <ul><li>Yeasts </li></ul><ul><li>Hyphae (filamentous fungi, mycelium) </li></ul><ul><ul><li>Septate </li></ul></ul><ul><ul><li>Coenocytic (non-septate) </li></ul></ul><ul><li>Dimorphic </li></ul><ul><ul><li>Yeast </li></ul></ul><ul><ul><li>Mycelium </li></ul></ul>www.freelivedoctor.com
  • 19. www.freelivedoctor.com
  • 20. www.freelivedoctor.com
  • 21. www.freelivedoctor.com
  • 22. Dimorphic Fungi <ul><li>Yeast Form </li></ul><ul><ul><ul><li>Parasitic form </li></ul></ul></ul><ul><ul><ul><li>Tissue form </li></ul></ul></ul><ul><ul><ul><li>Cultured at 37 C </li></ul></ul></ul><ul><li>Mycelial Form </li></ul><ul><ul><ul><li>Saprophytic form </li></ul></ul></ul><ul><ul><ul><li>Cultured at 25 C </li></ul></ul></ul>www.freelivedoctor.com
  • 23. SPORES <ul><li>SEXUAL </li></ul><ul><li>ASEXUAL </li></ul><ul><ul><li>Arthrospore </li></ul></ul><ul><ul><li>Blastospore </li></ul></ul><ul><ul><li>Chamydospore </li></ul></ul><ul><ul><li>Conidia </li></ul></ul><ul><ul><ul><li>Microconidia </li></ul></ul></ul><ul><ul><ul><li>Macroconidia </li></ul></ul></ul>www.freelivedoctor.com
  • 24. www.freelivedoctor.com
  • 25. www.freelivedoctor.com
  • 26. www.freelivedoctor.com
  • 27. C. EPIDEMIOLOGY www.freelivedoctor.com
  • 28. ECOLOGICAL ASSOCIATION <ul><li>PATHOGEN HUMAN SOIL </li></ul><ul><li>_________________________________________ </li></ul><ul><li>Blastomyces dermatitidis 1898 1964 </li></ul><ul><li>Cryptococcus neoformans 1894 1951 </li></ul><ul><li>Coccidioides immitis 1900 1932 </li></ul><ul><li>Histoplasma capsulatum 1934 1949 </li></ul>www.freelivedoctor.com
  • 29. Mycotic Diseases Are NOT Contagious www.freelivedoctor.com
  • 30. ESTABLISHMENT OF INFECTION WITH A MYCOTIC AGENT DEPENDS ON <ul><li>Inoculum size </li></ul><ul><li>Resistance of the host </li></ul>www.freelivedoctor.com
  • 31. www.freelivedoctor.com
  • 32. THE CLINICIAN MUST DISTINGUISH BETWEEN: <ul><li>COLONIZATION </li></ul><ul><li>FUNGEMIA </li></ul><ul><li>INFECTION </li></ul>www.freelivedoctor.com
  • 33. PORTAL OF ENTRY EYE SKIN UROGENITAL TRACT ANUS MOUTH RESPIRATORY TRACT <ul><li>SKIN </li></ul><ul><li>HAIR </li></ul><ul><li>NAILS </li></ul><ul><li>RESPIRATORY TRACT </li></ul><ul><li>GASTROINTESTINAL TRACT </li></ul><ul><li>URINARY TRACT </li></ul>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 <ul><li>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. </li></ul>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 <ul><li>10 % KOH </li></ul><ul><li>Gentle Heat </li></ul>www.freelivedoctor.com
  • 42. www.freelivedoctor.com
  • 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 ) <ul><li>Use is limited to : </li></ul><ul><ul><li>Determine cellular defense mechanisms </li></ul></ul><ul><ul><li>Epidemiologic studies </li></ul></ul>www.freelivedoctor.com
  • 46. www.freelivedoctor.com
  • 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 <ul><li>Latex Agglutination IgM </li></ul><ul><li>Immunodiffusion IgG </li></ul><ul><li>Complement Fixation IgG </li></ul>www.freelivedoctor.com
  • 50. www.freelivedoctor.com
  • 51. DIRECT FLUORESCENT ANTIBODY CAN BE APPLIED TO <ul><li>HISTOLOGIC SECTIONS </li></ul><ul><li>CULTURE </li></ul><ul><ul><li>Viable organisms </li></ul></ul><ul><ul><li>Non-viable organisms </li></ul></ul>www.freelivedoctor.com
  • 52. www.freelivedoctor.com
  • 53. INCUBATION TEMPERATURE <ul><li>37 C - Body temperature </li></ul><ul><li>25 C - Room temperature </li></ul>www.freelivedoctor.com
  • 54. E. TREATMENT www.freelivedoctor.com
  • 55. THERAPY <ul><li>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. </li></ul>www.freelivedoctor.com
  • 56. A BASIC TENET OF PATHOLGY : <ul><li>A CAUSE OF IRREVERSIBLE CELL INJURY IS CELL MEMBRANE DAMAGE. </li></ul>www.freelivedoctor.com
  • 57. IN FUNGAL THERAPY <ul><li>We attempt to induce cell injury by causing the cell membrane of the fungus to become permeable. </li></ul>www.freelivedoctor.com
  • 58. PRIMARY ANTI-FUNGAL AGENTS <ul><li>Polyene derivatives </li></ul><ul><ul><li>Amphotericin B </li></ul></ul><ul><ul><li>Nystatin </li></ul></ul><ul><li>Azoles </li></ul><ul><ul><li>Ketoconazole </li></ul></ul><ul><ul><li>Fluconazole </li></ul></ul><ul><ul><li>Itraconazole </li></ul></ul><ul><ul><li>Voriconazole </li></ul></ul><ul><ul><li>Posaconazole </li></ul></ul>www.freelivedoctor.com
  • 59. AMPHOTERICIN B Mechanism of Action <ul><li>Amphotericin B binds to sterols </li></ul><ul><li>Ergosterol is a constituent of the fungal cell wall </li></ul><ul><li>AMB has a greater avidity for ergosterol than for the cholesterol in the human cell wall </li></ul><ul><li>Binding to the fungal cell wall alters the permeability and the intracellular contents leak </li></ul>www.freelivedoctor.com
  • 60. AMPHOTERICIN B Disadvantages <ul><li>Intravenous administration </li></ul><ul><li>Thrombophlebitis </li></ul><ul><li>Nephrotoxic </li></ul><ul><li>Fever </li></ul><ul><li>Chills </li></ul><ul><li>Anemia </li></ul><ul><li>Long term administration </li></ul>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 <ul><li>3. Griseofulvin </li></ul><ul><li>4. 5-fluorocytosine (5-FC) </li></ul><ul><li>5. Allylamines </li></ul><ul><li>-Terbinafine (Lamasil) </li></ul><ul><li>6. Echinocandins </li></ul><ul><li>- Caspofungin </li></ul>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 <ul><li>Polyenes </li></ul><ul><li>Azoles </li></ul><ul><li>Griseofulvin </li></ul><ul><li>5 - FC </li></ul><ul><li>Ergosterol in cell membrane </li></ul><ul><li>Interfere with ergosterol synthesis </li></ul><ul><li>Forms a barrier to fungal growth </li></ul><ul><li>Inhibits RNA synthesis </li></ul>www.freelivedoctor.com
  • 66. F. Clinical Classification of Mycoses <ul><li>Cutaneous </li></ul><ul><li>Subcutaneous </li></ul><ul><li>Systemic </li></ul><ul><li>Opportunistic </li></ul>www.freelivedoctor.com
  • 67. Cutaneous Mycoses <ul><li>Skin, hair and nails </li></ul><ul><li>Rarely invade deeper tissue </li></ul><ul><li>Dermatophytes </li></ul>www.freelivedoctor.com
  • 68. Subcutaneous Mycoses <ul><li>Confined to subcutaneous tissue and rarely spread systemically. The causative agents are soil organisms introduced into the extremities by trauma </li></ul>www.freelivedoctor.com
  • 69. Systemic Mycoses <ul><li>Involve skin and deep viscera </li></ul><ul><li>May become widely disseminated </li></ul><ul><li>Predilection for specific organs </li></ul>www.freelivedoctor.com

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