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OPPORTUNISTIC FUNGAL INFECTIONS. Smilja Kalenic, MD, PhD Clinical Hospital Centre Zagreb, Croatia. LEARNING AND PERFORMANCE OBJECTIVES to learn about the most frequent opportunistic fungi and to understand main risk factors for developing infection
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OPPORTUNISTIC FUNGAL INFECTIONS Smilja Kalenic, MD, PhD Clinical Hospital Centre Zagreb, Croatia
LEARNING 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 preventively
FUNGI • EUCARIOTIC ORGANISMS • TWO BASIC FORMS: - YEASTS - MOLDS
MYCOSES 1. SUPERFICIAL 2. CUTANEOUS 3. SUBCUTANEOUS
MYCOSES 4. ENDEMIC (PRIMARY, SYSTEMIC): Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Paracoccidioides brasiliensis
MYCOSES 5.OPPORTUNISTIC endogenous - Candida (different species) - Pneumocystis carinii (?)
MYCOSES 5.OPPORTUNISTIC exogenous - Cryptococcus neoformans - Aspergillus (different species) - Zygomycetes - MANY OTHER FUNGI
Candida albicans and other Candida species • Harmless inhabitants of the skin and mucous membranes of all humans • Normal immune system keeps candida on body surfaces
MAIN DEFENSE MECHANISMS AGAINST CANDIDA I. • skin and mucous membranes integrity • presence of normal bacterial flora
MAIN DEFENSE MECHANISMS AGAINST CANDIDA II. • phagocytosis • killing, mostly in polymorphonuclear cells, less in macrophages • T-cells (CD4)
THE MOST IMPORTANT RISK FACTORS 1. Neutropenia 2. Diabetes mellitus 3. AIDS 4. SCID 5. Myeloperoxidase defects 6. Broad-spectrum antibiotics
THE MOST IMPORTANT RISK FACTORS 7. Indwelling catethers 8. Major surgery 9. Organ transplantation 10. Neonates 11. Severity of any illness 12. Intravenous drug addicts
CLINICAL FORMS OF CANDIDIASIS 1. Cutaneous and mucosal candidiasis
CLINICAL FORMS OF CANDIDIASIS 2. Invasive (systemic, disseminated, hematogenous) candidiasis
INVASIVE CANDIDIASIS • Usually begins with candidemia (but in only about 50% of cases candidemia can be proven) • If phagocytic system is normal, invasive infection stops here
INVASIVE 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 diagnosis
EPIDEMIOLOGY Although 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 infection
Pneumocystis carinii • Main defense mechanism is T-cell mediated • causes interstitial pneumonitis in compromised patients • treatment and prevention: cotrimoxasole or pentamidine
Cryptococcus neoformans • Occurs worldwide in soil and in bird droppings • Prominent feature: thick polysaccharide capsule, which causes evasion from phagocytosis
MAIN DEFENSE MECHANISMS AND PATHOGENESIS • T-cells responsible for defense • Cryptococcus reaches humans by inhalation of aerosolized yeast cells
CHRONIC MENINGITIS IN AIDS-PATIENTS • The most important clinical syndrome • treatment: amphotericin B+/-flucytosine • recurrence prevention: fluconazole
EPIDEMIOLOGY OF CRYPTOCOCCOSIS Infection is always exogenous, is not transmitted from human to human
Aspergillus 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 transplantation • and corticosteroid therapy
The most frequent syndromes are: - aspergilloma - invasive aspergillosis (high mortality rate) Treatment: amphotericin B, itraconazole, flucytosine and surgery Prevention: 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 therapy
Major clinical syndrome is: Rhinocerebral mucormycosis (infection of nasal passages, sinuses, eyes, cranial bones and brain) Treatment: surgery and amphotericin B Prognosis: very poor
OPPORTUNISTIC 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 fields