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5 Opportunistic

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

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