1. Opportunistic Mycoses Infections due to fungi of low virulence in patients who are immunologically compromised

2. Medical Mycology Iceberg

3. PATHOGENIC FUNGI NORMAL HOST Systemic pathogens- 25 species Cutaneous pathogens- 33 species Subcutaneous pathogens- 10 species IMMUNOCOMPROMISED HOST Opportunistic fungi- 300 species

4. HOST-PATHOGEN EQUILIBRIUM NUMBER OF ORGANISMS X VIRULENCE =DISEASE HOST RESISTANCE

5. Opportunistic Fungi 1. Saprophytic - from the environment 2. Endogenous – a commensal organism

6. Opportunistic Fungi Include many species from: A (Aspergillus) To Z (Zygomyces)

7. MOST SERIOUS OPPORTUNISTIC INFECTIONS CANDIDA SPECIES ASPERGILLUS SPECIES MUCOR SPECIES (ZYGOMYCES)

8. Upward Trend In Opportunistic Mycoses 1.Increased clinical awareness 2.Improved clinical diagnostic tools 3.Improved laboratory diagnostic technics 4.An increase in susceptible hosts. 5.More invasive diagnostic and therapeutic procedures

9. Must distinguish between 1.Transient fungemia 2.Colonization 3.Infection

10. Transient fungemia The fortuitous isolation of a commensal or environmental organism

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

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

13. Predisposing Factors Malignancies Leukemias Lymphomas Hodgkins Disease

14. Predisposing Factors Drug therapies Anti-neoplastics Steroids Immunosuppressive drugs

15. Predisposing Factors Antibiotics Over-use or inappropriate use of antibiotics alter the normal flora allowing fungal overgrowth

16. Predisposing Factors Therapeutic procedures Solid organ or bone marrow transplant Open heart surgery Indwelling catheters Artificial heart valves Radiation therapy

17. Predisposing Factors Other Factors Severe burns Diabetes Tuberculosis IV Drug use

18. Predisposing Factors AIDS

19. Human Immunodeficiency Virus (HIV) HIV destroys the CD4 helper T cells

20. CD4 helper T cells are the basis of cell mediated immunity and play a role in host defenses against fungal diseases ERGO

21. Virtually all AIDS patients will have a fungal infection sometime during the course of their illness

22. BIOFILMS A POLYSACCHARIDE SLIME WHICH IS A MICROCOLONY OF ORGANISMS CONTAINING CHANNELS TO BRING IN NUTRIENTS AND CARRY OFF WASTE

26. Diagnosis of opportunistic infections requires a high index of suspicion 1.Atypical signs or symptoms 2.Unusual organ affinity 3.Outside the endemic area 4.Unusual Histopathology 5.Etiologic agent may be a saprophyte

27. CLINICAL PRESENTATION 1.Atypical Signs and Symptoms 2.Unusual Organ Affinity 3.Outside Endemic Area 4.Unusual histopathology 5.Unusual Pathogens

28. NORMAL PATIENT Malasezzia furfur Tinea versicolor (mild disease)

31. COMPROMISED PATIENTS Malasezzia furfur can cause disseminated infection--------Particularly in patients receiving hyperalimentation.

32. COMPROMISED IMMUNE SYSTEM Malasezzia furfur NUMBER OF ORGANISMS x LOW VIRULENCE = DISEASE HOST RESISTANCE

34. CLINICAL PRESENTATION 1.Atypical Signs and Symptoms 2.Unusual Organ Affinity 3.Outside Endemic Area 4.Unusual histopathology 5.Unusual Pathogens

35. Candida species Endogenous

36. Normal Flora The population of microorganisms that may be found residing in or on the human body without causing disease.

37. COMPETENT IMMUNE SYSTEM Candida albicans NUMBER OF ORGANISMS x VIRULENCE = NO DISEASE HOST RESISTANCE

38. COMPROMISED IMMUNE SYSTEM Candida albicans NUMBER OF ORGANISMS = DISEASE HOST RESISTANCE

41. IMMUNOCOMPROMISED PATIENTS CAN DEVELOP HEPATIC CANDIDIASIS

43. Candida species In the previous lecture I only mentioned Candida albicans. There are several Candida species that infect the compromised host.

44. Candida species C. glabrata C. krusei C. torulopsis C. parapsilosis C. lusitaniae C. dubliniensis

45. Cryptococcosis A sub-acute or chronic infection which may affect the lungs or skin but most commonly manifests as a meningitis

46. Ecological Niche Cryptococcus neoformans pigeon droppings Chicken droppings

47. Cryptococcus neoformans PORTAL OF ENTRY INHALATION INOCULATION

55. Cryptococcus neoformans LOW NUMBER X HIGH VIRULENCE = NO DISEASE NORMAL HOST

56. Cryptococcus neoformans LOW NUMBER X HIGH VIRULENCE = INFECTION COMPROMISED HOST

57. Cryptococcosis In the Compromised patient: Amphotericin B 5 FC Then Fluconazole the remainder of their life. Fluconazole penetrates the CSF

60. SPOROTRICHOSIS Primarily a disease of the cutaneous tissue and lymph nodes. Recently, pulmonary disease.

61. PORTALS OF ENTRY Inhalation Inoculation

63. ECOLOGICAL ASSOCIATIONS Rose thorns Sphagnum moss Timbers Soil

64. SPOROTRICHOSIS

67. 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

68. Aspergillus species HIGH NUMBER X LOW VIRULENCE = NO DISEASE NORMAL HOST

69. Aspergillus species LOW NUMBER X LOW VIRULENCE = INFECTION COMPROMISED HOST

72. CLINICAL PRESENTATION 1.Atypical Signs and Symptoms 2.Unusual Organ Affinity 3.Outside Endemic Area 4.Unusual histopathology 5.Unusual Pathogens

73. AIDS Patient Pneumocystis pneumonia Disseminated coccidioidomycosis (not pulmonary) Mycelial forms in abscesses (not spherules) Outside the endemic area (St. Louis, MO)

74. Spherules

76. HISTOPLASMOSIS IN AIDS PATIENTS ALL CASES ARE DISSEMINATED RELAPSES ARE GREATER THAN 50 % RAPIDLY FATAL IN 10 %

77. AIDS Patients Disseminated histoplasmosis (not pulmonary disease) New York City (outside the endemic region)

81. CLINICAL PRESENTATION 1.Atypical Signs and Symptoms 2.Unusual Organ Affinity 3.Outside Endemic Area 4.Unusual Histopathology 5.Unusual Pathogens

82. INFLAMMATORY REACTION NORMAL HOST –PYOGENIC –GRANULOMATOUS IMMUNODEFICIENT HOST –NECROTIC

83. CLINICAL PRESENTATION 1.Atypical Signs and Symptoms 2.Unusual Organ Affinity 3.Outside Endemic Area 4.Unusual histopathology 5.Unusual Pathogens

84. Opportunistic Fungi Include many species from: A (Aspergillus) To Z (Zygomyces)

85. Penicillium marneffei 1.Usually not a pathogen 2.The only dimorphic penicillium 3.Produces a red pigment 4.Endemic in the Far East

90. Pneumocystis jiroveci Recently confirmed as a member of Kingdom Fungi. Formerly thought to be a protozoan.

92. Cryptococcus neoformans Diabetes mellitus Tuberculosis Lymphoma Hodgkin’s disease Corticosteroid therapy Immunosuppression

93. Candida albicans Prolonged antibiotic therapy Prolonged intravenous therapy Prolonged urinary catheters Corticosteroid therapy Diabetes mellitus Hyperalimentation Immunosuppression

94. Torulopsis (Candida) glabrata Cytotoxic drugs Immunosuppression Diabetes mellitus Hyperalimentation Intravenous catheters

96. Mucormycetes Diabetes mellitus Leukemias Corticosteroid therapy Intravenous therapy Severe burns

97. Aspergillus species Leukemias Corticosteroid therapy Tuberculosis Immunosuppression Intravenous drug abuse

98. IMPROVING TREATMENT 1.New Drugs 2.New therapeutic regimen 3.Aggressive therapy 4.Conjunctive therapy

99. IMPROVING TREATMENT New Drugs Lipid Amphotericin B Third generation azoles (Posaconazole, Voriconazole) New classes of antifungal agents (Echinocandins)

100. IMPROVING TREATMENT New Therapeutic Regimen Combination Therapy 1.Simultaneously administering two drugs 2.Sequential Tx with two or more drugs 3.Alternate Administration of two or more

101. IMPROVING TREATMENT AGGRESSIVE THERAPY FOR IMMUNOCOMPROMISED PATIENTS 1.Prophylactic – Anti-fungal agents at, or near, the time of chemotherapy. 2.Posaconazole now approved.

102. 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.

103. IMPROVING TREATMENT AGGRESSIVE THERAPY FOR IMMUNOCOMPROMISED PATIENTS 3. Pre-emptive –When there is some additional evidence of fungal infection (serology, isolate, etc.)

104. IMPROVING TREATMENT CONJUNJUNCTIVE THERAPY Antifungal agent plus a recombinant monoclonal antibody.

105. IMPROVING TREATMENT CONJUNJUNCTIVE THERAPY FOR IMMUNOCOMPROMISED PATIENTS The use of anti-fungal agents with immunotherapy.

106. Immunotherapy Interferons Colony stimulating factors Interleukins

115. “In the field of observation, chance only favors those who are prepared.” Louis Pasteur - 1854 From: Inaugural Address as Professor of Chemistry and Dean of Faculty of Science, Lillie, France. “In the field of observation, chance only favors those who are prepared.” Louis Pasteur -1854

116. “Only the prepared mind can help the impaired host” Libero Ajello, Chief Mycology Division, CDC 1972

117. MYCOLGISTS have more FUN GI