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 HOSTOpportunistic 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 ALBICANSMorphology and Identification

• In culture or tissue, oval, budding yeast cells

• Pseudohyphae formation- chains of elongated cells that are constricted at the septations between cells

CANDIDAMorphology and Identification

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

CANDIDAMorphology and Identification

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

CANDIDAClinical Findings

• CUTANEOUS and

MUCOSAL CANDIDIASIS

- oral thrush

- vulvovaginitis

- cutaneous – intertriginous infections

- onychomycosis

CANDIDAClinical Findings

CANDIDAClinical Findings

• SYSTEMIC CANDIDIASIS

• CHRONIC MUCOCUTANEOUS CANDIDIASIS

CANDIDADiagnostic Laboratory Tests

A. Specimens : swabs and scrapings from superficial lesions, blood, spinal fluid, tissue biopsies, urine, exudates, catheters

B. Microscopic Examination: using KOH, demonstrate the presence of pseudohyphae in scrapings or tissue specimens

C. Culture : 37oC; presence of pseudohyphaeD. 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

CANDIDATreatment

• 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

ASPERGILLUSEpidemiology

• Distributed worldwide

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

ASPERGILLUSMorphology and Identification

• Produce conidial structure: long condiosphores with terminal vesicles on which phialides are seen

ASPERGILLUSPortal of Entry

INHALATION

ASPERGILLUSClinical Types

• Allergic – hypersensitivity to the organism

- respiratory symptoms may be

mild to alveolar fibrosis

ASPERGILLUSClinical 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

ASPERGILLUSClinical Types

• Aggressive tissue invasion

- primarily a pulmonary disease but aspergilli disseminate to any organ

- may cause endocarditis, osteomyelitis, otomycosis, and cutaneous

ASPERGILLUSDiagnostic Laboratory Tests

• Specimens : sputum, other respiratory specimens, or lung biopsy

• Microscopic Examination: with KOH, presence of hyaline branching septate hyphae

ASPERGILLUSDiagnostic 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

ASPERGILLUSDiagnostic Laboratory Tests

• SEROLOGY1. 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%)

ASPERGIILUSTreatment

AMPHOTERICIN B

MUCORMYCOSIS

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

MUCORMYCOSIS

Order Mucorales of the class

Zygomycetes1. Rhizopus species

2. Mucor species

3. Absidia species

MUCORMYCOSISEpidemiology

• 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

MUCORMYCOSISDiagnostic Laboratory Tests

• CULTURE• Grow rapidly on lab

media producing abundant cottony colonies.

MUCORMYCOSISDiagnostic Laboratory Tests

• DIRECT EXAMINATION:

- broad hyphae with uneven thickness, irregular branching and sparse septations

MUCORMYCOSISTreatment

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 NEOFORMANSMorphology and Identification

• Spherical cells that produce buds, charac-

teristic narrow-based

• Polysaccharide capsule surrounds the organism

• Capsule may suppress T-cell function – virulence factor

• Phenoloxidase (melanin) – also a virulent factor

CRYPTOCOCCUS NEOFORMANSPathogenesis

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 NEOFORMANSClinical Findings

1. Meningoencephalitis

- prolonged clinical course: begin with visual problems;

headache,neck stiffnessm coma, death

2. Skin and lung infections- formation of a granulomatous reaction with giant cells

- Cryptococcoma: mass in the mediastinum

CRYPTOCOCCUS NEOFORMANSDiagnostic 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 NEOFORMANSLaboratory Findings

• Cryptococcus neoformans in sputum,

Wright Stain

CRYPTOCOCCUS NEOFORMANSlaboratory findings

• Cryptococcus neoformans in blood culture, Gram stain

CRYPTOCOCCUS NEOFORMANSTreatment

• 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

1. New Drugs

2. New therapeutic regimen

3. Aggressive therapy

4. Conjunctive therapy

IMPROVING TREATMENT

New Drugs

Echinocandins

Third generation azoles

New classes of antifungal agents

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

IMPROVING TREATMENT

AGGRESSIVE THERAPY

FOR IMMUNOCOMPROMISED PATIENTS

1. 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