1 A Introduction

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1 A Introduction

  1. 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. 2. INTRODUCTION www.freelivedoctor.com
  3. 3. A. Classification www.freelivedoctor.com
  4. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 17. B. MORPHOLOGY www.freelivedoctor.com
  18. 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. 19. www.freelivedoctor.com
  20. 20. www.freelivedoctor.com
  21. 21. www.freelivedoctor.com
  22. 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. 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. 24. www.freelivedoctor.com
  25. 25. www.freelivedoctor.com
  26. 26. www.freelivedoctor.com
  27. 27. C. EPIDEMIOLOGY www.freelivedoctor.com
  28. 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. 29. Mycotic Diseases Are NOT Contagious www.freelivedoctor.com
  30. 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. 31. www.freelivedoctor.com
  32. 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. 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. 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. 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. 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. 37. Endemic Mycoses Those fungus infections with a limited geographic distribution. They are all caused by dimorphic fungi www.freelivedoctor.com
  38. 38. D. DIAGNOSIS www.freelivedoctor.com
  39. 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. 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. 41. DIRECT MICROSCOPIC OBSERVATION <ul><li>10 % KOH </li></ul><ul><li>Gentle Heat </li></ul>www.freelivedoctor.com
  42. 42. www.freelivedoctor.com
  43. 43. KOH Wet Mount www.freelivedoctor.com
  44. 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. 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. 46. www.freelivedoctor.com
  47. 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. 48. FUNGI ARE POOR ANTIGENS www.freelivedoctor.com
  49. 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. 50. www.freelivedoctor.com
  51. 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. 52. www.freelivedoctor.com
  53. 53. INCUBATION TEMPERATURE <ul><li>37 C - Body temperature </li></ul><ul><li>25 C - Room temperature </li></ul>www.freelivedoctor.com
  54. 54. E. TREATMENT www.freelivedoctor.com
  55. 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. 56. A BASIC TENET OF PATHOLGY : <ul><li>A CAUSE OF IRREVERSIBLE CELL INJURY IS CELL MEMBRANE DAMAGE. </li></ul>www.freelivedoctor.com
  57. 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. 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. 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. 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. 61. Azoles There are a few rare serious side effects from Itraconazole and Fluconazole www.freelivedoctor.com
  62. 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. 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. 64. 5- fluorocytosine (5-FC) Interferes With RNA Synthesis www.freelivedoctor.com
  65. 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. 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. 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. 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. 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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