Opportunistic Mycoses

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Opportunistic Mycoses

  1. 1. Opportunistic Mycoses <ul><li>Infections due to fungi of low virulence in patients who are immunologically compromised </li></ul>www.freelivedoctor.com
  2. 2. Medical Mycology Iceberg www.freelivedoctor.com
  3. 3. 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
  4. 4. HOST-PATHOGEN EQUILIBRIUM <ul><li>NUMBER OF ORGANISMS X VIRULENCE = DISEASE HOST RESISTANCE </li></ul>www.freelivedoctor.com
  5. 5. Opportunistic Fungi <ul><li>1. Saprophytic - from the environment </li></ul><ul><li>2. Endogenous – a commensal organism </li></ul>www.freelivedoctor.com
  6. 6. Opportunistic Fungi <ul><li>Include many species from: </li></ul><ul><li>A (Aspergillus) </li></ul><ul><li>To </li></ul><ul><li>Z (Zygomyces) </li></ul>www.freelivedoctor.com
  7. 7. MOST SERIOUS OPPORTUNISTIC INFECTIONS <ul><li>CANDIDA SPECIES </li></ul><ul><li>ASPERGILLUS SPECIES </li></ul><ul><li>MUCOR SPECIES (ZYGOMYCES) </li></ul>www.freelivedoctor.com
  8. 8. Upward Trend In Opportunistic Mycoses <ul><li>Increased clinical awareness </li></ul><ul><li>Improved clinical diagnostic tools </li></ul><ul><li>Improved laboratory diagnostic technics </li></ul><ul><li>An increase in susceptible hosts. </li></ul><ul><li>More invasive diagnostic and therapeutic procedures </li></ul>www.freelivedoctor.com
  9. 9. Must distinguish between <ul><li>Transient fungemia </li></ul><ul><li>Colonization </li></ul><ul><li>Infection </li></ul>www.freelivedoctor.com
  10. 10. Transient fungemia <ul><li>The fortuitous isolation of a commensal or environmental organism </li></ul>www.freelivedoctor.com
  11. 11. 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
  12. 12. 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
  13. 13. Predisposing Factors <ul><li>Malignancies </li></ul><ul><li>Leukemias </li></ul><ul><li>Lymphomas </li></ul><ul><li>Hodgkins Disease </li></ul>www.freelivedoctor.com
  14. 14. Predisposing Factors <ul><li>Drug therapies </li></ul><ul><li>Anti-neoplastics </li></ul><ul><li>Steroids </li></ul><ul><li>Immunosuppressive drugs </li></ul>www.freelivedoctor.com
  15. 15. Predisposing Factors <ul><li>Antibiotics </li></ul><ul><li>Over-use or inappropriate use of antibiotics alter the normal flora allowing fungal overgrowth </li></ul>www.freelivedoctor.com
  16. 16. Predisposing Factors <ul><li>Therapeutic procedures </li></ul><ul><li>Solid organ or bone marrow transplant </li></ul><ul><li>Open heart surgery </li></ul><ul><li>Indwelling catheters </li></ul><ul><li>Artificial heart valves </li></ul><ul><li>Radiation therapy </li></ul>www.freelivedoctor.com
  17. 17. Predisposing Factors <ul><li>Other Factors </li></ul><ul><li>Severe burns </li></ul><ul><li>Diabetes </li></ul><ul><li>Tuberculosis </li></ul><ul><li>IV Drug use </li></ul>www.freelivedoctor.com
  18. 18. Predisposing Factors <ul><li>AIDS </li></ul>www.freelivedoctor.com
  19. 19. Human Immunodeficiency Virus (HIV) HIV destroys the CD4 helper T cells www.freelivedoctor.com
  20. 20. CD4 helper T cells are the basis of cell mediated immunity and play a role in host defenses against fungal diseases ERGO www.freelivedoctor.com
  21. 21. <ul><li>Virtually all AIDS patients will have a fungal infection sometime during the course of their illness </li></ul>www.freelivedoctor.com
  22. 22. BIOFILMS <ul><li>A POLYSACCHARIDE SLIME WHICH IS A MICROCOLONY OF ORGANISMS CONTAINING CHANNELS TO BRING IN NUTRIENTS AND CARRY OFF WASTE </li></ul>www.freelivedoctor.com
  23. 23. Diagnosis of opportunistic infections requires a high index of suspicion <ul><li>Atypical signs or symptoms </li></ul><ul><li>Unusual organ affinity </li></ul><ul><li>Outside the endemic area </li></ul><ul><li>Unusual Histopathology </li></ul><ul><li>Etiologic agent may be a saprophyte </li></ul>www.freelivedoctor.com
  24. 24. CLINICAL PRESENTATION <ul><li>Atypical Signs and Symptoms </li></ul><ul><li>Unusual Organ Affinity </li></ul><ul><li>Outside Endemic Area </li></ul><ul><li>Unusual histopathology </li></ul><ul><li>Unusual Pathogens </li></ul>www.freelivedoctor.com
  25. 25. NORMAL PATIENT <ul><li>Malasezzia furfur </li></ul><ul><li>Tinea versicolor </li></ul><ul><li>(mild disease) </li></ul>www.freelivedoctor.com
  26. 26. www.freelivedoctor.com
  27. 27. www.freelivedoctor.com
  28. 28. COMPROMISED PATIENTS <ul><li>Malasezzia furfur can cause disseminated infection--------Particularly in patients receiving hyperalimentation. </li></ul>www.freelivedoctor.com
  29. 29. COMPROMISED IMMUNE SYSTEM Malasezzia furfur NUMBER OF ORGANISMS x LOW VIRULENCE = DISEASE HOST RESISTANCE www.freelivedoctor.com
  30. 30. www.freelivedoctor.com
  31. 31. CLINICAL PRESENTATION <ul><li>Atypical Signs and Symptoms </li></ul><ul><li>Unusual Organ Affinity </li></ul><ul><li>Outside Endemic Area </li></ul><ul><li>Unusual histopathology </li></ul><ul><li>Unusual Pathogens </li></ul>www.freelivedoctor.com
  32. 32. Candida species Endogenous www.freelivedoctor.com
  33. 33. Normal Flora <ul><li>The population of microorganisms that may be found residing in or on the human body without causing disease. </li></ul>www.freelivedoctor.com
  34. 34. COMPETENT IMMUNE SYSTEM Candida albicans NUMBER OF ORGANISMS x VIRULENCE = NO DISEASE HOST RESISTANCE www.freelivedoctor.com
  35. 35. COMPROMISED IMMUNE SYSTEM Candida albicans NUMBER OF ORGANISMS = DISEASE HOST RESISTANCE www.freelivedoctor.com
  36. 36. www.freelivedoctor.com
  37. 37. www.freelivedoctor.com
  38. 38. IMMUNOCOMPROMISED PATIENTS CAN DEVELOP HEPATIC CANDIDIASIS www.freelivedoctor.com
  39. 39. www.freelivedoctor.com
  40. 40. Candida species <ul><li>In the previous lecture I only mentioned Candida albicans . There are several Candida species that infect the compromised host. </li></ul>www.freelivedoctor.com
  41. 41. Candida species <ul><li>C. glabrata </li></ul><ul><li>C. krusei </li></ul><ul><li>C. torulopsis </li></ul><ul><li>C. parapsilosis </li></ul><ul><li>C. lusitaniae </li></ul><ul><li>C. dubliniensis </li></ul>www.freelivedoctor.com
  42. 42. Cryptococcosis <ul><li>A sub-acute or chronic infection which may affect the lungs or skin but most commonly manifests as a meningitis </li></ul>www.freelivedoctor.com
  43. 43. Ecological Niche Cryptococcus neoformans <ul><li>pigeon droppings </li></ul><ul><li>Chicken droppings </li></ul>www.freelivedoctor.com
  44. 44. Cryptococcus neoformans PORTAL OF ENTRY <ul><li>INHALATION </li></ul><ul><li>INOCULATION </li></ul>www.freelivedoctor.com
  45. 45. www.freelivedoctor.com
  46. 46. www.freelivedoctor.com
  47. 47. www.freelivedoctor.com
  48. 48. www.freelivedoctor.com
  49. 49. www.freelivedoctor.com
  50. 50. www.freelivedoctor.com
  51. 51. www.freelivedoctor.com
  52. 52. Cryptococcus neoformans LOW NUMBER X HIGH VIRULENCE = NO DISEASE NORMAL HOST www.freelivedoctor.com
  53. 53. Cryptococcus neoformans LOW NUMBER X HIGH VIRULENCE = INFECTION COMPROMISED HOST www.freelivedoctor.com
  54. 54. Cryptococcosis <ul><li>In the Compromised patient: </li></ul><ul><li>Amphotericin B </li></ul><ul><li>5 FC </li></ul><ul><li>Then Fluconazole the remainder of their life. </li></ul><ul><li>Fluconazole penetrates the CSF </li></ul>www.freelivedoctor.com
  55. 55. www.freelivedoctor.com
  56. 56. www.freelivedoctor.com
  57. 57. SPOROTRICHOSIS Primarily a disease of the cutaneous tissue and lymph nodes. Recently, pulmonary disease. www.freelivedoctor.com
  58. 58. PORTALS OF ENTRY <ul><li>Inhalation </li></ul><ul><li>Inoculation </li></ul>www.freelivedoctor.com
  59. 59. www.freelivedoctor.com
  60. 60. ECOLOGICAL ASSOCIATIONS <ul><li>Rose thorns </li></ul><ul><li>Sphagnum moss </li></ul><ul><li>Timbers </li></ul><ul><li>Soil </li></ul>www.freelivedoctor.com
  61. 61. SPOROTRICHOSIS www.freelivedoctor.com
  62. 62. www.freelivedoctor.com
  63. 63. Blastomycosis in AIDS patients <ul><li>One report </li></ul><ul><li>16 Patients </li></ul><ul><li>10 localized disease </li></ul><ul><ul><li>7-lung, 2-skin, 1 CNS </li></ul></ul><ul><li>6 Disseminated </li></ul><ul><ul><li>5/6 – CNS </li></ul></ul><ul><li>All did poorly </li></ul>www.freelivedoctor.com
  64. 64. Aspergillus species HIGH NUMBER X LOW VIRULENCE = NO DISEASE NORMAL HOST www.freelivedoctor.com
  65. 65. Aspergillus species LOW NUMBER X LOW VIRULENCE = INFECTION COMPROMISED HOST www.freelivedoctor.com
  66. 66. www.freelivedoctor.com
  67. 67. www.freelivedoctor.com
  68. 68. CLINICAL PRESENTATION <ul><li>Atypical Signs and Symptoms </li></ul><ul><li>Unusual Organ Affinity </li></ul><ul><li>Outside Endemic Area </li></ul><ul><li>Unusual histopathology </li></ul><ul><li>Unusual Pathogens </li></ul>www.freelivedoctor.com
  69. 69. AIDS Patient <ul><li>Pneumocystis pneumonia </li></ul><ul><li>Disseminated coccidioidomycosis </li></ul><ul><li>(not pulmonary) </li></ul><ul><li>Mycelial forms in abscesses </li></ul><ul><li>(not spherules) </li></ul><ul><li>Outside the endemic area </li></ul><ul><li>(St. Louis, MO) </li></ul>www.freelivedoctor.com
  70. 70. Spherules www.freelivedoctor.com
  71. 71. www.freelivedoctor.com
  72. 72. HISTOPLASMOSIS IN AIDS PATIENTS <ul><li>ALL CASES ARE DISSEMINATED </li></ul><ul><li>RELAPSES ARE GREATER THAN 50 % </li></ul><ul><li>RAPIDLY FATAL IN 10 % </li></ul>www.freelivedoctor.com
  73. 73. AIDS Patients <ul><li>Disseminated histoplasmosis </li></ul><ul><li> (not pulmonary disease) </li></ul><ul><li>New York City </li></ul><ul><li>(outside the endemic region) </li></ul>www.freelivedoctor.com
  74. 74. www.freelivedoctor.com
  75. 75. www.freelivedoctor.com
  76. 76. www.freelivedoctor.com
  77. 77. CLINICAL PRESENTATION <ul><li>Atypical Signs and Symptoms </li></ul><ul><li>Unusual Organ Affinity </li></ul><ul><li>Outside Endemic Area </li></ul><ul><li>Unusual Histopathology </li></ul><ul><li>Unusual Pathogens </li></ul>www.freelivedoctor.com
  78. 78. INFLAMMATORY REACTION <ul><li>NORMAL HOST </li></ul><ul><ul><li>PYOGENIC </li></ul></ul><ul><ul><li>GRANULOMATOUS </li></ul></ul><ul><li>IMMUNODEFICIENT HOST </li></ul><ul><ul><li>NECROTIC </li></ul></ul>www.freelivedoctor.com
  79. 79. CLINICAL PRESENTATION <ul><li>Atypical Signs and Symptoms </li></ul><ul><li>Unusual Organ Affinity </li></ul><ul><li>Outside Endemic Area </li></ul><ul><li>Unusual histopathology </li></ul><ul><li>Unusual Pathogens </li></ul>www.freelivedoctor.com
  80. 80. Opportunistic Fungi <ul><li>Include many species from: </li></ul><ul><li>A (Aspergillus) </li></ul><ul><li>To </li></ul><ul><li>Z (Zygomyces) </li></ul>www.freelivedoctor.com
  81. 81. Penicillium marneffei <ul><li>Usually not a pathogen </li></ul><ul><li>The only dimorphic penicillium </li></ul><ul><li>Produces a red pigment </li></ul><ul><li>Endemic in the Far East </li></ul>www.freelivedoctor.com
  82. 82. www.freelivedoctor.com
  83. 83. www.freelivedoctor.com
  84. 84. www.freelivedoctor.com
  85. 85. www.freelivedoctor.com
  86. 86. Pneumocystis jiroveci Recently confirmed as a member of Kingdom Fungi. Formerly thought to be a protozoan. www.freelivedoctor.com
  87. 87. www.freelivedoctor.com
  88. 88. Cryptococcus neoformans <ul><li>Diabetes mellitus </li></ul><ul><li>Tuberculosis </li></ul><ul><li>Lymphoma </li></ul><ul><li>Hodgkin’s disease </li></ul><ul><li>Corticosteroid therapy </li></ul><ul><li>Immunosuppression </li></ul>www.freelivedoctor.com
  89. 89. Candida albicans <ul><li>Prolonged antibiotic therapy </li></ul><ul><li>Prolonged intravenous therapy </li></ul><ul><li>Prolonged urinary catheters </li></ul><ul><li>Corticosteroid therapy </li></ul><ul><li>Diabetes mellitus </li></ul><ul><li>Hyperalimentation </li></ul><ul><li>Immunosuppression </li></ul>www.freelivedoctor.com
  90. 90. Torulopsis (Candida) glabrata <ul><li>Cytotoxic drugs </li></ul><ul><li>Immunosuppression </li></ul><ul><li>Diabetes mellitus </li></ul><ul><li>Hyperalimentation </li></ul><ul><li>Intravenous catheters </li></ul>www.freelivedoctor.com
  91. 91. www.freelivedoctor.com
  92. 92. Mucormycetes <ul><li>Diabetes mellitus </li></ul><ul><li>Leukemias </li></ul><ul><li>Corticosteroid therapy </li></ul><ul><li>Intravenous therapy </li></ul><ul><li>Severe burns </li></ul>www.freelivedoctor.com
  93. 93. Aspergillus species <ul><li>Leukemias </li></ul><ul><li>Corticosteroid therapy </li></ul><ul><li>Tuberculosis </li></ul><ul><li>Immunosuppression </li></ul><ul><li>Intravenous drug abuse </li></ul>www.freelivedoctor.com
  94. 94. IMPROVING TREATMENT <ul><li>New Drugs </li></ul><ul><li>New therapeutic regimen </li></ul><ul><li>Aggressive therapy </li></ul><ul><li>Conjunctive therapy </li></ul>www.freelivedoctor.com
  95. 95. IMPROVING TREATMENT <ul><li>New Drugs </li></ul><ul><li>Lipid Amphotericin B </li></ul><ul><li>Third generation azoles </li></ul><ul><li>(Posaconazole, Voriconazole) </li></ul><ul><li>New classes of antifungal agents </li></ul><ul><li>(Echinocandins) </li></ul>www.freelivedoctor.com
  96. 96. IMPROVING TREATMENT <ul><li>New Therapeutic Regimen </li></ul><ul><li>Combination Therapy </li></ul><ul><li>Simultaneously administering two drugs </li></ul><ul><li>Sequential Tx with two or more drugs </li></ul><ul><li>Alternate Administration of two or more </li></ul>www.freelivedoctor.com
  97. 97. IMPROVING TREATMENT <ul><li>AGGRESSIVE THERAPY </li></ul><ul><li>FOR IMMUNOCOMPROMISED PATIENTS </li></ul><ul><li>Prophylactic – Anti-fungal agents at, or near, the time of chemotherapy. </li></ul><ul><li>Posaconazole now approved. </li></ul>www.freelivedoctor.com
  98. 98. IMPROVING TREATMENT <ul><li>AGGRESSIVE THERAPY </li></ul><ul><li>FOR IMMUNOCOMPROMISED PATIENTS </li></ul><ul><li>2. Empirical – Start therapy when patient at risk, i.e., fever and/or infiltrate without response to anti-bacterials. </li></ul>www.freelivedoctor.com
  99. 99. IMPROVING TREATMENT <ul><li>AGGRESSIVE THERAPY </li></ul><ul><li>FOR IMMUNOCOMPROMISED PATIENTS </li></ul><ul><li>3. Pre-emptive – When there is some additional evidence of fungal infection (serology, isolate, etc.) </li></ul>www.freelivedoctor.com
  100. 100. IMPROVING TREATMENT <ul><li>CONJUNJUNCTIVE THERAPY </li></ul><ul><li>Antifungal agent plus a recombinant monoclonal antibody. </li></ul>www.freelivedoctor.com
  101. 101. IMPROVING TREATMENT <ul><li>CONJUNJUNCTIVE THERAPY </li></ul><ul><li>FOR IMMUNOCOMPROMISED PATIENTS </li></ul><ul><li>The use of anti-fungal agents with immunotherapy. </li></ul>www.freelivedoctor.com
  102. 102. Immunotherapy <ul><li>Interferons </li></ul><ul><li>Colony stimulating factors </li></ul><ul><li>Interleukins </li></ul>www.freelivedoctor.com

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