Opportunistic Fungi

Opportunistic Mycoses

Infections due to fungi of low virulence in patients who are immunologically compromised

PATHOGENIC FUNGI •

NORMAL HOST • • •

•

Systemic pathogens - 25 species Cutaneous pathogens - 33 species Subcutaneous pathogens - 10 species

IMMUNOCOMPROMISED HOST Opportunistic fungi

- 300 species

MOST FREQUENT OPPORTUNISTIC INFECTIONS • • • •

CANDIDA SPECIES ASPERGILLUS SPECIES MUCOR SPECIES CRYPTOCOCCUS

CANDIDA SP. • Endogenous organism • Found in 40-80% of normal human beings – present in the mouth, skin, gut and vagina • May be commensal or pathogenic • Frequently infects skin and mucosa but can also cause pneumonia, septicemia or endocarditis in immunocompromised hosts

CANDIDA ALBICANS Morphology and Identification • In culture or tissue, oval, budding yeast cells • Pseudohyphae formation- chains of elongated cells that are constricted at the septations between cells

CANDIDA Morphology and Identification • On blood agar, after 24 hours of incubation , moist opaque colonies are seen with yeasty odor

CANDIDA Morphology and Identification • Germ tube or true hyphae formation distinguish Candida albicans from the rest of Candida sp.

CANDIDA Clinical Findings • CUTANEOUS and MUCOSAL CANDIDIASIS - oral thrush - vulvovaginitis - cutaneous – intertriginous infections - onychomycosis

CANDIDA Clinical Findings

CANDIDA Clinical Findings • SYSTEMIC CANDIDIASIS • CHRONIC MUCOCUTANEOUS CANDIDIASIS

CANDIDA Diagnostic Laboratory Tests • • • •

Specimens : swabs and scrapings from superficial lesions, blood, spinal fluid, tissue biopsies, urine, exudates, catheters Microscopic Examination: using KOH, demonstrate the presence of pseudohyphae in scrapings or tissue specimens Culture : 37oC; presence of pseudohyphae Serology: not useful; lack sensitivity and specificity

CANDIDA SP. Diagnostic Laboratory Tests GERM TUBE TEST - rapid screening test where the production of germ tubes by the cells is diagnostic for Candida albicans

CANDIDA Treatment

• For mucocutaneous form: topical nystatin, ketoconazole, fluconazole • For systemic infection: Amphotericin B

ASPERGILLUS • Ubiquitous saprophyte • A fumigatus – most common human pathogen • Produces abundant conidia – easily aerosolized which can be inhaled and invade the lungs

ASPERGILLUS Epidemiology

• Distributed worldwide • Commonly found in soil, food, paint, air vents, disinfectants

ASPERGILLUS Morphology and Identification • Produce conidial structure: long condiosphores with terminal vesicles on which phialides are seen

ASPERGILLUS Portal of Entry

INHALATION

ASPERGILLUS Clinical Types • Allergic – hypersensitivity to the organism - respiratory symptoms may be mild to alveolar fibrosis

ASPERGILLUS Clinical Types • Fungus ball (Aspergilloma) – recognized by x-ray, may be mistaken for TB cavity • A colony of saprophytic mold growing in preformed cavity usually due to TB or sarcoidosis • Patients cough up the fungus elements

ASPERGILLUS Clinical Types • Aggressive tissue invasion - primarily a pulmonary disease but aspergilli disseminate to any organ - may cause endocarditis, osteomyelitis, otomycosis, and cutaneous

ASPERGILLUS Diagnostic Laboratory Tests • Specimens : sputum, other respiratory specimens, or lung biopsy • Microscopic Examination: with KOH, presence of hyaline branching septate hyphae

ASPERGILLUS Diagnostic Laboratory Tests • Culture - require 1-3 weeks for growth - assumes a variety of colors - species differentiation is based on spore formation as well as their color, shape and texture

ASPERGILLUS Diagnostic Laboratory Tests • SEROLOGY 1. Immunodiffusion test – antibody detection - presence of precipitin bands (5) - presence of 3 or more bands indicate more severe disease 2. EIA to measure galactomannan - highly specific (99%) but less sensitive (50%)

ASPERGIILUS Treatment

AMPHOTERICIN B

MUCORMYCOSIS • ACUTE INFLAMMATION OF SOFT TISSUE, USUALLY FUNGAL INVASION OF THE BLOOD VESSELS

MUCORMYCOSIS Order Mucorales of the class Zygomycetes 1. Rhizopus species 2. Mucor species 3. Absidia species

MUCORMYCOSIS Epidemiology • World-wide distribution • Common in soil, food, organic debris, seen on decaying vegetables in the refrigerator and on moldy bread • Rhinocerebral infection – major clinical form • Frequently seen in the uncontrolled diabetic

MUCORMYCOSIS Clinical Finding • Rhinocerebral infection: - invasion of the sinuses, eyes, cranial bones and brain - blood vessels are damaged, facial edema, bloody nasal exudate, orbital cellulitis

MUCORMYCOSIS Diagnostic Laboratory Tests • CULTURE • Grow rapidly on lab media producing abundant cottony colonies.

MUCORMYCOSIS Diagnostic Laboratory Tests • DIRECT EXAMINATION: - broad hyphae with uneven thickness, irregular branching and sparse septations

MUCORMYCOSIS Treatment Surgical debridement Rapid administration of amphotericin B Control of underlying disease

CRYPTOCOCCUS NEOFORMANS • Yeast with a thick polysaccharide capsule • Occurs worldwide in nature • Found in very large numbers in dry pigeon and chicken droppings

CRYPTOCOCCUS NEOFORMANS Morphology and Identification • Spherical cells that produce buds, characteristic narrow-based • Polysaccharide capsule surrounds the organism • Capsule may suppress Tcell function – virulence factor • Phenoloxidase (melanin) – also a virulent factor

CRYPTOCOCCUS NEOFORMANS Pathogenesis INHALATION OF YEAST CELLS(AEROSOLIZED) ↓ PRIMARY PULMONARY INFECTION (asymptomatic or flu-like illness) ↓ In immunocompromised, may disseminate to other organs preferentially to the CNS (meningoencephalitis)

CRYPTOCOCCUS NEOFORMANS Clinical Findings 1. Meningoencephalitis - prolonged clinical course: begin with visual problems; headache,neck stiffnessm coma, death

4. Skin and lung infections - formation of a granulomatous reaction with giant cells - Cryptococcoma: mass in the mediastinum

CRYPTOCOCCUS NEOFORMANS Diagnostic Laboratory Tests • Specimens: spinal fluid, exudates, blood, urine, sputum

• INDIA INK TEST – demonstrates capsule of this yeast

Latex Agglutination test for antigen - decreasing titer indicates a good prognosis

CRYPTOCOCCUS NEOFORMANS Laboratory Findings

• Cryptococcus neoformans in sputum, Wright Stain

CRYPTOCOCCUS NEOFORMANS laboratory findings

• Cryptococcus neoformans in blood culture, Gram stain

CRYPTOCOCCUS NEOFORMANS Treatment

• AMPHOTERICIN B

Predisposing Factors Malignancies • Leukemias • Lymphomas • Hodgkins Disease

Predisposing Factors Drug therapies • Anti-neoplastics • Steroids • Immunosuppressive drugs

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

Predisposing Factors

• • • • •

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

Predisposing Factors

• • • •

Other Factors Severe burns Diabetes Tuberculosis IV Drug use

Predisposing Factors

AIDS

Some Common Associations between fungal organisms and Disease Condition CRYPTOCOCCUS -

Diabetes melllitus tuberculosis lymphoma Hodgkin’s disease steroid therapy immunosuppression

Some Common Associations between fungal organisms and Disease Condition CANDIDA -

prolonged antibiotic therapy prolonged IV catheter prolonged urinary catheter corticosteroid therapy Diabetes mellitus hyperalimentation immunosuppression

Some Common Associations between fungal organisms and Disease Condition ASPERGILLUS - leukemia -

corticosteroid therapy tuberculosis immunosuppression IV drug use

Some Common Associations between fungal organisms and Disease Condition ZYGOMYCETES (MUCOR) -

diabetes mellitus leukemia steroid therapy IV therapy severe burns

IMPROVING TREATMENT

3. 4. 5. 6.

New Drugs New therapeutic regimen Aggressive therapy Conjunctive therapy

IMPROVING TREATMENT New Drugs Echinocandins Third generation azoles New classes of antifungal agents

IMPROVING TREATMENT New Therapeutic Regimen Combination Therapy 4. Simultaneously administering two drugs 5. Sequential Tx with two or more drugs 6. Alternate Administration of two or more

IMPROVING TREATMENT AGGRESSIVE THERAPY FOR IMMUNOCOMPROMISED PATIENTS •

Prophylactic – Anti-fungal agents at, or near, the time of chemotherapy

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.

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

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

Immunotherapy • Interferons • Colony stimulating factors • Interleukins

MYCOLGISTS have more

FUNGI