Slide 1Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30OPPORTUNISTIC FUNGAL INFECTIONSSmilja Kalenic, MD, PhDClinical Hospital Centre Zagreb, CroatiaLEARNING AND PERFORMANCE OBJECTIVES• to learn about the most frequent opportunistic fungi and to understand main risk factors for developing infection• to be able to predict the most probable agent of invasive fungal infection in a particular compromised patient state and to be able to act preventivelyFUNGI•EUCARIOTIC ORGANISMS•TWO BASIC FORMS:- YEASTS - MOLDSMYCOSES1. SUPERFICIAL2. CUTANEOUS3. SUBCUTANEOUSMYCOSES4. ENDEMIC (PRIMARY, SYSTEMIC): Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Paracoccidioides brasiliensisMYCOSES5. OPPORTUNISTICendogenous - Candida (different species)- Pneumocystis carinii (?)MYCOSES5. OPPORTUNISTICexogenous- Cryptococcus neoformans- Aspergillus (different species)- Zygomycetes- MANY OTHER FUNGICandida albicans and other Candida species•Harmless inhabitants of the skin and mucous membranes of all humans•Normal immune system keeps candida on body surfacesMAIN DEFENSE MECHANISMS AGAINST CANDIDA I.•skin and mucous membranes integrity•presence of normal bacterial floraMAIN DEFENSE MECHANISMS AGAINST CANDIDA II.•phagocytosis•killing, mostly in polymorphonuclear cells, less in macrophages•T-cells (CD4)THE MOST IMPORTANT RISK FACTORS1. Neutropenia2. Diabetes mellitus 3. AIDS4. SCID 5. Myeloperoxidase defects 6. Broad-spectrum antibioticsTHE MOST IMPORTANT RISK FACTORS7. Indwelling catethers8. Major surgery9. Organ transplantation10. Neonates11. Severity of any illness12. Intravenous drug addictsCLINICAL FORMS OF CANDIDIASIS1. Cutaneous and mucosal candidiasisCLINICAL FORMS OF CANDIDIASIS2. Invasive (systemic, disseminated, hematogenous) candidiasisINVASIVE CANDIDIASIS•Usually begins with candidemia (but in only about 50% of cases candidemia can be proven)•If phagocytic system is normal, invasive infection stops hereINVASIVE CANDIDIASIS•If phagocytic system is compromised, infection spreads to many organs and causes focal infection in these organs•mortality of candidemia is 30-40%DIAGNOSIS OF INVASIVE CANDIDIASIS•Gram stain and isolation from blood, CSF or peritoneal fluid•isolation and/or pathology positive of organ involved•other tests are of lower significance for the diagnosisEPIDEMIOLOGYAlthough candidiasis is endogenous in most cases, cross infections are described, especially in intensive care unit patients.Pneumocystis carinii•Present in lungs of many mammals, including humans, in persistent but harmless infectionPneumocystis carinii•Main defense mechanism is T-cell mediated•causes interstitial pneumonitis in compromised patients•treatment and prevention: cotrimoxasole or pentamidineCryptococcus neoformans•Occurs worldwide in soil and in bird droppings• Prominent feature: thick polysaccharide capsule, which causes evasion from phagocytosisMAIN DEFENSE MECHANISMS AND PATHOGENESIS•T-cells responsible for defense•Cryptococcus reaches humans by inhalation of aerosolized yeast cellsCHRONIC MENINGITIS IN AIDS-PATIENTS•The most important clinical syndrome•treatment: amphotericin B+/-flucytosine•recurrence prevention: fluconazoleEPIDEMIOLOGY OF CRYPTOCOCCOSISInfection is always exogenous, is not transmitted from human to humanAspergillus species•Aspergilli are worldwide occurring saprophytes, living in soil and on plants; they have small conidia that form aerosols• Main defense mechanism is phagocytosis• Main risk factors are hematological malignancy,bone marrow transplantationand corticosteroid therapyThe most frequent syndromes are: - aspergilloma- invasive aspergillosis (high mortality rate)Treatment: amphotericin B, itraconazole, flucytosine and surgeryPrevention: avoid exposure to conidia (new buildings in the hospital!)ZYGOMYCETES•Zygomycetes are ubiquitous saprophytes•main host defense is phagocytosis•main risk factors are diabetes, hematological malignancies, corticosteroid therapyMajor clinical syndrome is:Rhinocerebral mucormycosis (infection of nasal passages,sinuses, eyes, cranial bones and brain)Treatment: surgery andamphotericin BPrognosis: very poorOPPORTUNISTIC FUNGAL INFECTIONS ARE:•difficult to diagnose•difficult to treat•difficult to prevent•more and more frequent•a great challenge for a future work in all