OPPORTUNISTIC FUNGAL INFECTIONS Smilja Kalenic MD Ph D

OPPORTUNISTIC FUNGAL INFECTIONS Smilja Kalenic, MD, Ph. D 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 (CD 4)

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