Fungi

Fungi • Mycology: the study of fungi – Fungi are widespread in nature; ~200,000 species identified – Most fungi involved in decomposition of organic matter & play important role in recycling organic compounds in nature – Fungi are Eukaryotic organisms • Unicellular morphology (=Yeast) or Mulitcellular morphology (= Mold)

Fungi • Yeasts (Unicellular morphology) – Single, oval or spherical fungal cell – Reproduction: Asexual by budding – Budding • Division of nucleus • Passage of one nucleus to a bud the “balloons” out from the mother cell • Formation of wall between the bud and mother cell • Daughter cell = bud or blastospore • Daughter cell initially smaller than mother cell; but, it will increase in size & produce own buds

• Molds (Filamentous morphology) – Multicellular – filamentous or tubular structures – Reproduction: asexual or sexual (main discriminating feature)

Fungi • Growth of mold – Germination of Condium (=asexual reproductive unit in fungi) – send out a filament that grows by elongation @ its tip – Hyphae – elongated filament; the basic structure of growing molds – Mycelium – multiple branches of hypae; mass of hypae – Many nuclei located w/in each hypae – Formation of Septae = “cross-walls” w/in hypae – Conidia – terminal ends of hyphae; “seeds” for new colonies; molds reproduce by developing conidia on the hyphae

• Sexual reproduction – 2 reproductive bodies connect & haploid cells fuse to form diploid cells (spores) – meiosis – Resulting diploid cells become Spores = reproductive elements formed from sexual reproduction – Rare among the human fungal pathogens

Fungi Dimorphic Fungi

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Dimorphism: the property of having 2 morphological shapes; dimorphic fungi have capability of 2 distinct forms – dependent on temperature •

Temperature Dependent 1. Yeast form: 37°C 2. Mold or mycelial form: 25°C

General characteristics

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– Cell wall: rigid & thick; NO PG – 1° component is presence of sterol in cell wall – No locomotion: non-motile Distinguishing Morphological Characteristics –

Size, presence of a capsule, cell wall thickness, spores or conidia production

Fungi • Growth Conditions – – – –

Molds: aerobic Yeasts: facultative anaerobes Acid pH (4.0 → 6.0) Selective Laboratory Media • Sabouraud’s Dextrose Agar (SDA) – low pH • Dermatophyte Test Media (DTM) – turns red in presence of all dermatophytes • Birdseed Agar – specific for ID of Cryptococcus neoformans ( agar turns brown); all other Crytpococcus spp – turn it white

– Minimal Media • Corn Meal Agar (ID of spore formation: production of terminal conidia)

– Slide cultures – undisturbed growth – Colonial Morphology • Molds – dry, cotton-like masses • Yeast – moist, opaque, creamy colonies

Mycoses (Fungal Diseases) 1.

Superficial Mycoses • •

1.

“surface infection” Fungal diseases that grow on surface of skin & nails

Cutaneous Mycoses or Dermatomycoses •

1.

Fungal infections of keratinous structures – outer layers of skin, nails, in hair shafts

Subcutaneous Mycoses •

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Infections that penetrate below the skin & involve the subcutaneous CT and bone tissue

Systemic or Deep Mycoses •

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Infections of internal organs – from disseminated disease

Opportunistic Mycoses •

Infections in compromised or immunosuppressed

Dermatomycoses • ONLY contagious fungal infection/disease in humans; not associated w/ death, just uncomfortable symptoms and characteristic lesions • Dermatophytes – fungi that invade keratinized & cutaneous areas of the body – Nails, hair and skin

• 3 Major Genera – Microsporum – Tichophyton = m/c dermatophyte fungus – Epidermophyton

Dermatomycoses •

Mode of Infection –

Hyphae grows into keratinized tissues of epidermis, into hair shaft, or into finger/toe nail Growth outward from infection site in concentric circles Enzyme production – keratinase, elastase and collagenase

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Clinical Infections 1.

Tinea capitis (ringworm of scalp) – Trichophyton & Microsporum spp. – – –

Initial Sx: inflammation & itching of the scalp Mode of Infection: hypae spread into keratinized areas of scalp & hair follicle → fungal growth weakens the hair → breakage @ shaft → ALOPECIA (hair loss): localized & spotty Associated mostly w/ children (high transmission)

Dermatomycoses •

Clinical Infection 2.

Tinea Barbae (ringworm of the beard) – – – –

2.

Infection site – bearded areas Superficial lesion – scaly Severe infection – development of deep pustules Result – permanent hair loss

Tinea pedis (ringworm of the foot, “Athlete’s Foot”) – m/c in adolescents & adults – – – –

Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum Sx’s – foot lesions Mode of infection – growth between toes of small fluid-filled vesicles → vesicles rupture → development of shallow lesion that itch; may become infected with bacterial (2° bacterial infection) Predisposing conditions – public showers, swimming pools, failure to dry between toes.

Dermatomycoses •

Clinical Infections 4.

Tinea curis (ringworm of the groin, “Jock Itch”) – – –

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Tinea corporis (ringworm of the body) – – –

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E. floccosom & T. rubrum Sx’s – lesions in groin or perianal area → red, scaly, itchy and often dry Predisposing factors – moisture in the groin area; wet bathing suits, athletic supporter, tight fitting pants/slacks and obesity E. floccosum, spp. of Trichophyton & Microsporum Infection site – non-hairy areas of the body Sx’s – lesions are reddened, scaly, w/ papular eruptions

Tinea unguium (ringwom of nails - onychomycosis) – – – –

T. rubrum Infection sites – fingernails and toenails Initial Sx’s – superficial white patches on nail beds: puffy & chalky Later Sx’s – thickening of the nail, accumulation of cheesy debris, cracking and discoloration of the nail

Dermatomycoses • Diagnosis – Clinical signs and symptoms – Microscopic ID from tissue scraping samples: presence of hyphae • Tissue scraping + 10% KOH (heated, then stain added) → presence of septate hyphae visible under microscope

– Macroscopic ID • Culture: Dermatophyt Test Media (DTM) – turns RED • Culture: Sabouraud’s Dextrose Agar (SDA)

• Treatment – Non-Rx: salves/ointments – for symptomatic relief – Good hygiene – Oral antibiotic therapy – Topical antifungal agent Note: re-infection may occur over & over => not good host immune response

Subcutaneous Mycoses • • • •

Fungal source = normal inhabitants of soil or organic matter Introduction to host – wound or abrasions of skin Deeper infection – penetration to below skin Clinical Infections 1.

Sporotrichosis (“Rose Gardner’s Disease”) – –

1.

Causative agent = Sporothrix schenckii Mode of infection – traumatic implantation of fungus into skin → painless papule @ inoculation site → enlargement to form ulcerated lesion → then possible spread to regional lymph nodes = Lymphocutaneous sporotrichosis

Lymphocutaneous Sporotrichosis – –

Mode of infection – fungus form multiple nodules after being spread by draining lymph node channels → nodules may ulcerate → untreated lesions last for years Occupational Risk Groups = horticulturists, foresters, gardeners, farmers & basket weavers

Systemic Mycosis • “True pathogens” – infect normal, healthy individuals • “Opportunisitic pathogens” – infect debilitated +/or immunocompromised individuals • Mode of Infection – inhalation of spores → lower respiratory tract → germinate into yeast → asymptomatic or 1° pulmonary infection that parallels TB → disseminated to other organs d/t compromised defense mechanism • NO person-to-person transmission; only airborne route to humans from fungal spores – Fungi growing in soil or on an. droppings produce conidia that be aerosolized and carried by air-borne route to humans

Systemic Mycosis •

Clinical Diseases 1. Coccidioidomycosis – – – –

Chronic, necrotizing mycotic infection of the lungs; resembles TB pathologically Begins as a bronchopneumonia w/ its inflammatory infiltrate Disseminated to many site in immunocompromised pt’s: skin, bones, meninges, liver, spleen Causative agent: Coccidiodes immitis • • • •

Dimorphic fungus that grows in soil of SW US Spore = Arthrospores – inhaled into alveoli and terminal bronchi, where they enlarge into “spherules” Spherules fill w/ endospored, which are released to form more spherules In Arizona – 50% chance (after 10 yrs) person w/ (+) serology to this b/c of exposure, NOT necessarily the disease

Systemic Mycosis •

Clinical Diseases 1.

Coccidioidomycosis –

Epidemiology   

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Pathogenesis 

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SW US, particularly San Joaquin and Sacramento Valley of California, areas around Tucson and Phoenix in Arizona High incidence of infection & disease may follow dust storm Coccidioidomycosis = Valley Fever = San Joaquin Valley Fever = Desert Rheumatism Inhalation of arthroconidia leads to 1° infection • Asymptomatic in 60% individuals • 40%: self-limiting influenza-like illness – fever, malaise, cough, arthralgia, HA

Laboratory DX 1. 2. 3. 4.

Culture: specimen from sputum; exudate from cutaneous lesions; CSF, blood, urine, tissue biopsies Serology – IgM Ab detection w/ latex agglutination Coccidioidin Skin Test (+) Chest X-Ray analysis – hilar lymphadenopathy along w/ pulmonary infiltrates, pneumonia, pleural effusions or nodules

Systemic Mycosis •

Clinical Diseases 2.

Histoplamosis – – –

m/c fungal disease in US Acute, necrotizing, caseous granuloma of the lungs Causative agent = Histoplasma capsulatum  

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Fungus grows in soil → formation of conidia → airborne → inhalation into the lungs → germination into yeast-like cells → engulfed by alveolar macrophages Infection – acute, but benign and self-limiting; or chronic, progressive and fatal 

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Dimorphic fungus found in nature Multiplies extensively in areas where bird feces accumulate

Usu. Self-limiting flu-like syndrome (fever, chills, myalgia, HA, nonproductive cough

Dissemination = rare; but can occur – to reticuloendothelial tissues (liver, spleen, BM lymph nodes)

Systemic Mycosis •

Clinical Diseases 2. Hitoplasmosis –

Laboratory Dx  Culture – specimens include sputum, urine, scrapings from superficial lesions, BM aspirates  Microscopic examination of fungus in macrophages  Serology – Tests for Ab’s to Histoplasmin Ag or yeast cells  Skin Test – Histoplasmin (+)

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Epidemiology  most prevalent in Ohio & Mississippi River Valleys, including Central and Eastern States  KC = high risk area  Reservoir = Soils laden w/ bird, chicken, or bat droppings = rich sources of the fungus (natural habitat)

Systemic Mycosis •

Clinical Diseases 3. Blastomycosis – – –

Chronic granulomatous and suppurative disease of the lungs, resulting in small areas of consolidation Causative agent = Blastomyces dermatitidis Fungus produces microconidia in soil, which become airborne and inhaled in lungs  Germination into yeast cells  Dissemination is rare, but can occur – skin, bone, GU tract

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M/c in South Central and South Eastern US M/c clinical presentation = pulmonary infiltrate w/ fever, malaise, cough, myalgia, night sweats

Opportunistic Mycoses • Endogenous type infection – caused by normal flora of respiratory tract, mouth, intestinal tract and vagina • Opportunistic Infection – Overgrowth of normal flora → inflammation of epithelial surfaces (m/c = oral cavity and vagina) → dissemination to internal organs

Opportunistic Mycoses •

Clinical Diseases 1.

Cryptococcosis – – –

1° disease of lungs w/ granulomas and consolidation Rapidly spreads to the meninges and brain, causing meningoencephalitis Etiological agent = Cryptococcus neoformans  

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Epidemiology    

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Only systemic fungus that is NOT dimorphic Only true yeast unicellular pathogen of humans Occurs worldwide in nature; found in very large #’s in dry pigeon feces Usually associated w/ immunosuppression – AIDS, malignancy 2nd m/c fungal dis in AIDS pts (after candidiasis) Reservoir = decomposing plant materials (soil) w/ high N content from pigeon feces

Pathogenesis   

Inhalation of yeast cells (encapsulated, dry, easily aerosolized) Influenza-like illness follows Immunosupressed: yeast cells multiply and disseminated to CNS • YEAST CELLS FOUND W/IN CSF

Opportunistic Mycoses •

Clinical Diseases 1.

Cryptococcus – –

S/sx’s: MAJOR clinical manifestation = chronic meningitis w/ spontaneous remissions and exacerbations Pt presentation    

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Laboratory Dx   

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HA Stiff neck Disorientation Lesions in skin, lungs CSF pressure and protein [ ] ↑ WBC count ↑ Glucose [ ] normal or low

Diagnosis   

Specimens from CSF, sputum, blood, urine, exudates Culture Serology

Opportunistic Mycoses •

Clinical Diseases 2. Candidiasis (candidiosis) –

Causative agent = Candida albicans  Normal flora of skin, vagina, and intestines  Considered a yeast, but is Dimorphic (forms a true mycelium)

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Cutaneous Infections  arise d/t host’s condition – diabetes, immunological deficiencies, exposure of skin to moist environment  Mode of infection 1. Adherence to epithelial surfaces 2. Fungal proliferation 3. Invasion of epithelial tissue

Opportunistic Mycoses •

Cutaneous Infection w/ C. ablicans 1.

Thrush or Oral Candidiasis = Most Common Candidiasis –

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Symptomatic appearance: white, adherent patches (pseudomembranes) attach to epithelial membranes of tongue, gums, cheeks, or throat – FUNGAL MAT formation – Pseudomembrane composition = yeast, hyphae, epithelial debris – Increased susceptibility: Newborns – Transmission: Vertical - Mother→Child Vaginal Candidiasis = m/c form of vaginal infection – Sx’s: yellow to white milky discharge, inflammation, painful ulcerations & itching – Candidal overgrowth – related to increased glucose content of vaginal secretions – Assoc’d w/ - diabetic ♀, pregnant ♀, broad spectrum antibiotic tx

Opportunistic Mycoses •

Cutaneous Infection w/ C. ablicans 3. Esophageal Candidiasis – Complication of AIDS patients – Sx’s: painful bleeding, ulcerations, nausea, vomiting

3. General Candidiasis Infections – Infections of epidermal tissue – folds of skin on obese people (usual sites =upper legs, underarms); tissue that remains wet (dishwashers); skin covered by wet diapers (diaper rash)

Opportunistic Mycoses • Disseminated infection w/ C. albicans – Cutaneous infection → mutisystem disease – Iatrogenic – use of catheters of prosthetic devices

• Diagnosis – Clinical symptoms – Microscopic examination – Macroscopic examination – culture • SDA (white- to cream-colored colny, pasty w/ a yeasty odor • Corn Meal Agar – visualization of spores

• Treatment: Antifungals

Opportunistic Mycoses •

Clinical Diseases 3.

Asperigellosis – – –

3.

Causative agent = Aspergillus fumigatus Acute, invasive infection of lung – dissemination to brain, GIT, other organs Non-invasive lung infection gives rise to aspergilloma (Fungal Ball) – a mass of hyphal tissue that can form in lung cavities produced by other diseases, like TB

Pneumocystis Pneumonia – – – –

Causative agent = Pneumocystis jiroveci Pneumocystis carnii Acute interstitial pneumonia w/ plasma cell infiltrates As disease progresses, pt. experiences weakness, dyspnea, and tachypnea leading to cyanosis; Death can result from asphixiation m/c cause of DEATH in AIDS pts from Pneumocystis carinii pnuemonia