OPPORTUNISTIC MYCOSES By Dr Muhammad Kaleem Asst Prof

OPPORTUNISTIC MYCOSES By Dr Muhammad Kaleem Asst. Prof of Pathology MBBS MC Mirpur (AJK) For 3 rd Year MBBS

OPPORTUNISTIC MYCOSES Fungal exposure Immunocompromised Fungal disease Uninfected Healthy

OPPORTUNISTIC MYCOSES Endogenous Exogenous Candida & related yeasts. Others. Members of normal flora Soil-Water-Air

OPPORTUNISTIC MYCOSES • Patients with HIV/AIDS CD 4+ Lymphocyte count. • Opportunistic mycoses • CD 4+ < counts 200 cells/μL

OPPORTUNISTIC MYCOSES CAUSATIVE AGENTS Candidiasis Candida Spp. Cryptococcosis Cryptococcus Spp. Aspergillosis Aspergillus Spp. Mucormycosis Mucor Spp. Atypical pneumonia Pneumocystis jeroveci Penicilliosis Peniciliium marnifei

Candida Species 1. 2. 3. 4. 5. 6. 7. 8. C. albicans C. parapsilosis C. glabrata C. tropicalis C. krusei C. dubliniensis C. lusitaniae C. guilliermondii

Candida Species • C. krusei • C. lusitaniae azole-resistant species

Candida Species • Skin • Mucous membranes. • Gastrointestinal tract. Normal flora

CANDIDIASIS • Candida species. • Colonize mucosal surfaces of all humans soon after birth. • Risk of endogenous infection is ever present. • Most prevalent systemic mycosis.

Diseases Cutaneous infections Systemic

Morphology and Identification • • In culture or tissue Oval, budding yeast cells (3– 6 μm in size).

Morphology and Identification Pseudohyphae When the buds continue to grow but fail to detach, producing chains of elongated cells that are pinched or constricted at the septations between cells.

Morphology and Identification Dimorphic. Yeasts and pseudohyphae. C albicans Can also produce true hyphae.

Morphology and Identification C. glabrata • Unique among Candida Spp. • Produces only yeast cells • No pseudohyphal forms

On agar media OR within 24 hours at 37°C OR room temperature, Candida species Ø Soft, cream-colored colonies with a yeasty odor. Ø Pseudohyphae are apparent as submerged growth below the agar surface.

Morphologic tests • 2 tests that distinguish C albicans from other species of Candida. Ø Incubation in serum at 37°C for 90 minutes Ø Yeast cells of C albicans large, will begin to form chlamydospores Nutritionally deficient media. C albicans produces spherical

Sugar fermentation & assimilation tests Ø Identification. Ø Speciation.

Pathogenesis & Pathology 1. Superficial (cutaneous or mucosal) candidiasis 2. Systemic candidiasis

Superficial (cutaneous or mucosal) candidiasis Ø Increase in number of Candida locally. Ø Damage to the skin or epithelium.

Systemic candidiasis Ø Candida enters the bloodstream. Ø Phagocytic host defenses are inadequate to contain the growth and dissemination of the yeasts.

Systemic candidiasis Ø Kidneys. Ø Prosthetic heart valves. Ø Arthritis. Ø Meningitis. Ø Endophthalmitis.

H/P cutaneous or mucocutaneous lesions • characterized Pyogenic abscesses Ø Inflammatory reactions granulomas Ø Lesions cells. . chronic Budding yeast Pseudohyphae.

Important Structures Ø Polysaccharides. Host defenses Ø Proteins Attachment. Invasion Ø Glycoproteins

Cutaneous and Mucosal Candidiasis Thrush Vulvovaginitis infections Skin

Thrush Ø Pseudomembranous confluent lesion Patchy to Whitish Ø Epithelial cells, yeasts, and pseudohyphae. Ø Tongue Ø Lips Ø Gums Ø Palate

Cutaneous and Mucosal Candidiasis Ø Irritation Ø Pruritus Vulvovaginitis Ø Vaginal discharge

Cutaneous and Mucosal Candidiasis Skin Ø Trauma, burns, or maceration. Ø Obese & Diabetics. Ø Red & moist Ø May develop vesicles

Cutaneous and Mucosal Candidiasis Common areas Ø Moist, warm parts of body Axillae Groin Intergluteal Inframammary folds

Cutaneous & Mucosal Candidiasis Interdigital involvement Ø Repeated prolonged immersion in water. Ø Fingers • • • Homemakers Bartenders Cooks Vegetable handlers Fish handlers Most common

Cutaneous & Mucosal Candidiasis Onychomycosis Ø Nails & around nail plate. • • Painful Erythematous swelling Nail destruction Resemble pyogenic paronychia

Cutaneous & Mucosal Candidiasis Risk factors Ø Antibiotics Ø Corticosteroids Ø Diabetes Ø Patients with AIDS Ø Pregnancy Ø Young or old age Ø Birth control pills Ø Trauma (burns, maceration of the skin)

Systemic Candidiasis Yeasts eliminated Ø Normal host defense Transient candidemia Ø Abnormal host defense Distant lesions

Systemic Candidiasis Ø Kidney. Ø Skin (maculonodular lesions). Ø Eye. Ø Heart. Ø Meninges.

Systemic Candidiasis Candidal endocarditis • Associated with deposition and growth of the yeasts and pseudohyphae on prosthetic heart valves or vegetations.

Systemic Candidiasis Renal infections Ø UTI’s Ø Predisposing factors • Foley catheters • Diabetes • Pregnancy • Antibiotics

Systemic Candidiasis Chronic Mucocutaneous Candidiasis Ø Rare disease Ø Early childhood Ø Cellular immunodeficiencies & endocrinopathies Ø Superficial disfiguring infections

Systemic Candidiasis Risk factors Ø Indwelling catheters Ø Surgery Ø Intravenous drug abuse Ø Damage to the skin or gastrointestinal tract Ø Corticosteroids Ø Immunosuppressive agents

Diagnostic Laboratory Tests Specimens Ø Swabs and scrapings from superficial lesions Ø Blood Ø Spinal fluid Ø Tissue biopsies Ø Urine Ø Exudates Ø Material from removed intravenous catheters

Diagnostic Laboratory Tests Microscopic Examination Ø Gram-stained smears Ø Histopathologic slides Ø Ø Pseudohyphae and budding cells Ø Skin or nail scrapings are first placed in a drop of 10% KOH and calcofluor white

Diagnostic Laboratory Tests Culture Ø Fungal or bacteriologic media Ø At room temperature OR Ø At 37°C.

Diagnostic Laboratory Tests Ø Yeast colonies are examined for presence of pseudohyphae. Ø C. albicans germ tubes or chlamydospores.

Diagnostic Laboratory Tests Ø Other Candida isolates are speciated with battery of biochemical reactions. Ø Interpretation of positive cultures varies with specimen. Ø Positive cultures from normally sterile body sites are significant.

Diagnostic Laboratory Tests Urine culture Ø Diagnostic value of a quantitative urine culture depends on integrity of specimen & yeast census. Ø Contaminated Foley catheters may lead to “false-positive” urine cultures.

Diagnostic Laboratory Tests Blood cultures Ø Systemic candidiasis OR Ø Transient candidemia due to contaminated i/v line.

Diagnostic Laboratory Tests Sputum & Skin Cultures Sputum culture Skin lesions • No value • Part of oral flora Confirmatory

Diagnostic Laboratory Tests Serology • Limited specificity or sensitivity. • Serum antibodies and cell-mediated immunity are demonstrable in most people as a result of lifelong exposure to Candida. • In systemic candidiasis, antibody titers to various candidal antigens may be elevated, but there are no clear criteria for establishing a diagnosis serologically.

Diagnostic Laboratory Tests Serology Ø Detection of cell wall glacto-mannan Ø By latex agglutination test or an enzyme immunoassay Ø More specific Ø Low sensitivity

Diagnostic Laboratory Tests Serology Ø Detection of β- D-glucan Ø Found in cell walls of many fungi Ø Not specific for Candida Ø Can be helpful when considered with other laboratory and clinical data.

Treatment Thrush and other mucocutaneou s forms Systemic candidiasis Chronic mucocutaneou s candidiasis Patients with genetic cellular immune defect Topical nystatin or oral ketoconazole or fluconazole Amphoterici n B, sometimes in conjunction with oral flucytosine, fluconazole, or Responds Require well to oral lifelong ketoconazole treatment. and other azoles.