MYCOLOGY

General Characteristics
Nonmotile organisms that form hyphae or

spores. Cause an array of diseases including skin, lung, opportunistic, and systemic infection. Grows in Sabarouds agar. (a beef brothdextrose mixture) Membrane contains ergosterol and chitin. All fungi are heterotrophs (that is they require some preformed organic carbon source for growth).

 Fungi depend upon transport of soluble nutrients

across their cell membranes for survival . To obtain these soluble nutrients, fungi secrete degradative enzymes (for example, cellulases, proteases, nudeases, etc.) into their immediate environment. It is this ability that enables fungi to live saprophytically on organic waste. Therefore, the natural habitat of almost all fungi is soil or water containing decaying organic matter.

Modes of fungal growth

Most fungi exist in one of two basic morphologic

forms (that is either as a filamentous mold or a unicellular yeast). However, some fungi are dimorptlic (that is, they switch between these two forms in response to environmental conditions). 1. Filamentous (mold-tike) fungi: The vegetative body, or thallus, of the mold-like fungi is typically a mass of threads with many branches resembling a cotton ball. The threads, called hyphae, are actually tubular, that are partitioned into segments (septate), or are uninterrupted by crosswalls (nonseptate).

 2. Yeast-like fungi: These fungi exist as

populations of single unconnected, spheroid cells. They reproduce by budding.

Sporulation
Sporulation is the principal means by which fungi

reproduce and spread through the environment. Fungal spores are metabolically dormant, protected cells, released by the mycelium in enormous numbers. Spores can be generated either asexually or sexually

Systemic
Inhaled particles disseminate system-wide

through the bloodstream producing systemic symptoms involving several organs. Includes Histoplasma, Coccidioides, Blastomyces. All are dimorphic fungi (existing in two forms), can cause disseminated disease, and can be treated with fluconazole. All can be diagnosed with sputum cytology, sputum cultures on blood agar, special media, and peripheral blood cultures (Histoplasma, particularly).

Key Points
Antifungals target ergosterol synthesis and

function and are safe to use in humans because human cells do not contain ergosterol. Antibiotics that target peptidoglycans do not affect fungi because fungi lack peptidoglycans Important dimorphic fungi include Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis.

Life form of Fungi

Fungi exist in two forms: yeast and molds. Many fungi can be found in either life form, depending on the temperature at which they are growing.

COCCIDIOIDES IMMITIS
CHARACTERISTICS:

Found in the southwestern United States, known

as desert rheumatic fever or valley fever. Dimorphicarthroconidia and endospores. At 25C (room temperature), grows as cylindrical arthroconidia. At 37C (body temperature), grows as spherules in endospore (spores with spherules).

Arthroconidia are a type of fungal spores typically produced by segmentation of pre-existing fungal hyphae. spores

PATHOGENESIS
Reservoir: Soil. Transmission: Airborne. Arthroconidia inhaled, become endospores in body. CLINICAL SYMPTOMS Erythema nodosum Pneumonitis CNS involvement Arthritis AIDS patients: Meningitis, mucocutaneous lesion Pregnancy: Disseminated in third trimester

DIAGNOSIS & TREATMENT

Dimorphic yeast (no hyphae). Thick-walled spores. Granulomas. Biopsy showed endospores inside spherules, all inside giant cells( Spores). Rx: Cell-mediated immunity is required. Itraconazole for mild infections. Amphotericin B for severe without CNS involvement. Fluconazole for CNS involvement (good CNS penetration). PROGNOSIS Fair, but may be fatal for elderly.

HISTOPLASMA CAPSULATUM

CHARACTERISTICS Found in Mississippi River Valley carried in bird and cat droppings. At 25C, grows as hyphae with macronidia and micronidia. At 37C, found as yeast inside macrophages in the body. Not transmittable from person to person.

PATHOGENESIS
Reservoir: Soil and bird and bat droppings

contain spores. Transmission: Spores are inhaled from dust and not transmittable person to person. Macrophages phagocytose spores and carry them systemically. Budding yeast form inside macrophages causing local infections throughout the body. Infections are contained within granulomas and calcify.

CLINICAL SYMPTOMS
Asymptomatic in immunocompetent patient.

Systemic infection in immunocompromised

patient. Calcifi ed granulomas in tissues involved. Pneumonitis that appears similar to milliary TB. May involve liver, spleen, adrenals in immunocompromised patients.

DIAGNOSIS Dimorphic yeast Thick-walled spores Granulomas Small budding cells within macrophages on biopsy. Calcifi ed lung lesions; may become cavitary in chronic progressive form. TREATMENT Cell-mediated immunity required. Itraconazole for moderate infection. Amphotericin B for severe infection

BLASTOMYCES DERMATITIDIS
CHARACTERISTICS Found on the East Coast of the United States and Mexico. Rarest of all systemic mycoses. At 27C, found as hyphae with small conidia. At 37C, found as budding yeast with broad base in tissue. PATHOGENESIS Reservoir: Soil, rotten wood contains spores. Transmission: Inhaled spores. Spores form yeast in the body, causing local infections. Yeast spread systemically over time and granulomas throughout the body (lungs, bones, skin).

CLINICAL SYMPTOMS Ulcerating pimples, verrucous. Pneumonitis, night sweats, weight loss. Meninigitis Arthritis Does not reactivate DIAGNOSIS Dimorphic yeast Thick-walled spores Lung lesions do not calcify Granulomas

TREATMENT Cell-mediated immunity required. Itraconazole for moderate infection or meningeal involvement. Amphotericin B for severe infection without meningeal involvement. PROGNOSIS Poor, most severe of systemic mycoses.

PARACOCCIDIODES
CHARACTERISTICS: Found in Latin America Appears as multiple budding yeast often described as pilots wheel Affected population 90% male PATHOGENESIS Reservoir: Spores found in soil. Transmission: Inhalation of spores. CLINICAL SYMPTOMS Symptoms are similar to those of Coccidiodes.

DIAGNOSIS Dimorphic yeast Multiple buds, like spokes of a wheel or pilots wheel. TREATMENT Bactrim Amphotericin B Itraconazole PROGNOSIS Good.

Opportunistic
These fungi often cause symptoms only in

immunocompromised hosts.

CANDIDA ALBICANS
CHARACTERISTICS:

Found in natural flora of skin. Appear as pseudohyphae and budding yeast in

tissue biopsy. Common cause of yeast infection and skin infection in immunocompromised.

PATHOGENESIS
Reservoir: GI flora, endogenous to mucous

membrane and normal skin flora in moist areas. Growth: Forms germ tubes at 37C and pseudohyphae/true hyphae when invading tissue grows rapidly if not controlled. Antibiotic use, immunocompromise, and cancer increases risk of infection.

CLINICAL SYMPTOMS
In immunocompetent hosts:
Oral thrush Vaginiitis (yeast infection in diabetic women). Diaper rash

In immunocompromised hosts
Esophagiitis Cutaneous infectionoften found in moist areas like

underneath breasts or in skin folds (i.e., diaper rash). Disseminated systemic infection and septicemia. Endocarditis in IV drug users.

DIAGNOSIS Silver stain KOH stain for pseudohyphae, budding yeast. Germ testgrow in animal serum TREATMENT Nystatin/fluconazole for cutaneous infection. Amphotericin B for systemic infection. PROGNOSIS Good.

CRYPTOCOCCUS NEOFORMANS
Appears as budding yeast in India ink stain.

Urease-positive.
Thick polysaccharide capsule. Affects AIDS patients and SLE patients.

PATHOGENESIS
Reservoir: Pigeon and bird droppings. Transmission: Inhaled yeast from droppings, leading to lung infection. Spread hematogenously to CNS, causing meningitis, abscess formation, and increased intracranial pressure. Growth within Virchow-Robinson space (space between vessel wall and surrounding connective tissue). Affects people with poor T-cellmediated Ab immunity

CLINICAL SYMPTOMS Pneumonia. Fungemia. Meningitisforms abscesses, also increases intracranial pressure.

DIAGNOSIS Latex agglutination test for capsular antigen in blood. Soap bubble lesions. Budding yeast on India ink stain. Urease-positive. TREATMENT Amphotericin B plus fl ucytosine for meningitis. Fluconazole for lifetime suppression in AIDS patients. PROGNOSIS Poor.

PNEUMOCYSTIS JIROVECI
CHARACTERISTICS: Appears as dark ovoid sporozoites within cysts on silver stain. Frequently affects AIDS patients. Also may affect premature infants. PATHOGENESIS Transmission: Cyst is inhaled by most people in childhood, leading to an asymptomatic or mild pneumonia, then a latent infection in the lungs. In immunocompromised hosts: Uncontrolled growth and an inflammatory response, leading to pneumonia.

CLINICAL SYMPTOMS Pneumonitis. Classically may cause pneumothorax DIAGNOSIS Silver stain showing cysts containing dark oval bodies. TREATMENT Bactrim or pentamidine. Bactrim, aerosolized pentamidine, or dapsone for prophylaxis. PROGNOSIS Fair. Pneumocystis carinii pneumonia (PCP) prophylaxis is begun when CD4 count is less than 200.

ASPERGILLUS FUMIGATUS
CHARACTERISTICS (see Figure 5-37): Found in wheat stacks. Branching hyphae that branch at a 45 angle. Fruiting bodies at ends of hyphae. Affects neutropenic patients.

PATHOGENESIS
Reservoir: Mold grows on decaying vegetation.
Transmission: Spores are inhaled. May stimulate IgE response leading to

bronchospasm and allergic bronchopulmonary aspergillosis. May deposit in existing lung cavity and form aspergillous ball (aspergilloma). May invade lung tissue and bloodstream in the immunocompromised host and occlude blood vessels leading to pulmonary infarction.

CLINICAL SYMPTOMS
Various lung diseases, including fungus ball,

acute and chronic pneumonitis, and disseminated systemic disease. Pneumonitis often with hemoptysis. DIAGNOSIS Tissue biopsy reveals branching hyphae (branching at a 45 angle) with septae. Sputum culture shows radiating chains of spores. X-ray may detect aspergilloma. Overall, diagnosis is difficult.

TREATMENT Allergic bronchopulmonary aspergillosis: Corticosteroids, no antifungals needed. Aspergilloma: Surgery. Invasive aspergillosis: Amphotericin B. PROGNOSIS Depends on type of disease. For disseminated disease, prognosis is poor.

RHIZOPUS MUCOR
CHARACTERISTICS (see Figure 5-38) Branching hyphae that branch at 90 angle. Nonseptate hyphae. Afflicts diabetics and leukemia patients. PATHOGENESIS Reservoir: Spores in the environment. Transmission: Spores inhaled. In immunocompromised hosts, colonizes tissue and invades blood vessels, leading to necrosis (similar to Aspergillus).

 Aspergillus fumigatus and Rhizopus mucor

appear very similar but Aspergillus branches at 45 degrees while Rhizopus branches at 90 degrees.

CLINICAL SYMPTOMS Invasive rhinocerebral infection. Pneumonitis similar to Aspergillus. DIAGNOSIS Tissue biopsy shows branching hyphae (branching at 90 angle) without septae. Shows a broad ribbon-like growth pattern. TREATMENT Control of diabetes Surgery for rhinocerebral infections Amphotericin PROGNOSIS Fair

Cutaneous
MICROSPORUM CHARACTERISTICS Includes multiple types of fungi that infect the skin. Trichophyton and Epidermophyton affect the nails specifically. Trichophyton mentagrophytes affects the feet. Branching hyphae that are septate with arthroconidia and cross-walls.

PATHOGENESIS
Reservoir: Soil, animals, humans.
Transmission: Spread by contact with infected

individuals or animals. Colonizes keratinized epithelium (dead, horny layer) in warm, moist areas. Infection spreads centrifugally with curvy worm-like borders (ringworm). Fungal antigens are released from the hyphae and may induce delayed type hypersensitivity reaction (dermatophytoses: Inflammation, itching, scaly skin, pustules). Fungal antigens may diffuse systemically and cause dermaphytid reactions: Hypersensitivity responses

CLINICAL SYMPTOMS
Ringworm (tinea corporis): Ring lesion on the skin that appears to be spreading centrifugally. Athletes foot (tinea pedis). Jock itch (tinea cruris). Oncomycoses (tinea unguium): Nail infection, discoloration of nails. Body infection (tinea corporis).

DIAGNOSIS & TREATMENT

Skin scrapings allow keratin to be removed. Hyphae can be observed on KOH prep. Woods lamp (UV) detects Microsporum. Topical antifungal creams for skin infections (imidazole). Oral antifungals for hair follicle and nail infections.

PROGNOSIS Good

1. Tinea pedis (athlete's foot):

Trichophyton rubrum, Trichophyton mentagrophytes,

and Epidermophyton floccosum. initially between the toes, but can spread to the nails, which become yellow and brittle. Another manifestation of rinia pedis is the "id" reaction (from dermatophytid), in which skin lesions (vesicles) develop at sites distant from the infected area, for example, on the hands. It has been speculated the the id reaction is due 10 circulating fungal antigens.

2. Tinea corporis (ringworm):

Epidermophyton floccosum,

and several species of Trichophyton and Microsporum. Lesions appear as advancing annular rings with scaly centers. The periphery of the ring, which is the site of active fungal growth is usually inflamed and vesiculated.

3. Tinea capitis (scalp ringworm):

Trichophyton and Microsporum

In the United States. the

predominant infecting species is Trichophyton tonsurans. Disease manifestations range from small, scaling patches, to involvement of the entire scalp with extensive hair loss. The hair shafts themselves can become invaded by Microsporum hyphae. as manifested by their green fluorescerce in long-wave

4. Tinea cruris ("jock itch"):

Causative organisms are

Epidermophyton floccosum, and Trichophyton rubrum. Disease manifestations are similar to ringworm, except that lesions occur in the moist groin area, where they can spread from the upper thighs to the genitals

5. Tinea unguium (onychomycosis):

Trichophyton rubrum.

The nails are

thickened, discolored, and brittle. Treatment must be continued for three to four months until all infected portions of the nail grow out and are trimmed off.

MALESSEZIA FURFUR
CHARACTERISTICS : Appears as spaghetti and meatballs on KOH prep. Causes pityriasis versicolor. PATHOGENESIS Reservoir: Animals, humans, soil. Transmission: Contact. CLINICAL SYMPTOMS Pityriasis versicolor: Pale spots on the skin, often on the back.

DIAGNOSIS KOH prep. Short, unbranched hyphae. Spherical yeast. Spaghetti and meatballs. PROGNOSIS Good. TREATMENT Topical antifungals: Imidazole.

Subcutaneous Mycosis
1. SPOROTHRIX SHENCKII
CHARACTERISTICS:

Found in soil. Gardeners nodule: Often

transmitted via prick of finger on rose thorns. At 25C, appears as branching hyphae with macronidia shapedlike flowers. At 37C, appears as unequally budding yeast.

PATHOGENESIS
Reservoir: Spores in soil.

Transmission: Spores enter skin through cuts

and puncture wounds such as puncture of rose thorn. Slow local infection forms primary nodule that becomes necrotic and ulcerates. Secondary nodules form along lymphatic tracts draining primary infections. is a dimorphic fungus that exhibits the yeast form in infected tissue

CLINICAL SYMPTOMS Subcutaneous nodules form along lymphatics usually in the upper extremity that was infected via break in the skin. DIAGNOSIS Culture at different temperatures reveals branched hyphae at 25C and single cells (cigarshaped budding yeast) at 37C. Produces black pigment. Rosette conidia. Neutrophilic microabscesses in skin.

TREATMENT Oral potassium iodide (mechanism unclear). Antifungals for extracutaneous involvement: Aphotericin B, itraconazole. PROGNOSIS Good

2. Chromomycosis (also called chromoblastomycosis):

This jnfection is characterized by warty nodules

that spread slowly along the lymphatics, and develop crusty abscesses. The pathogens causing this mycosis include several species of pigmented soil fungi, for example, Phialophora and Cladosporium. Treatment is difficult. Surgical removal of small lesions is effective, but must be performed cautiously and with wide margins to prevent dissemination. More advanced stages of the disease are treated with oral flucytosine combined with the anti helminthic drug, thiabendazole.

3. Mycetoma (Madura foot):

Mycetoma appears as a localized abscess, usually

on the feet, that discharges pus, serum, and blood through sinuses. The infection can spread to the underlying bone and result in crippling deformaties. The pathogenic agents are various soil fungi or actinomycetes(bacteria). Most common are Madurella grisea and Actinomadura madurae. Characteristic of mycetoma is the presence of colored grains, composed of compacted hyphae, in the exudate. The color of the grains (black. white, red, or yellow) is characteristic of the causative organism.

Protozoa