Mycology and Parasitology

Candida and Malassezia, which are part of the normal flora

Chytridiomycosis caused by Batrachonchytrium dendrobatidis.

Uses keratin as nutrient --> hyperkeratosis + excessive shedding

Fungus that causes chytridiomycosis = wiping out the global amphibian species. Endemic among African clawed frog.

Uses keratin as nutrient --> hyperkeratosis + excessive shedding

Aggressive wheat fungus that is putting world's wheat crop in danger.

1. plasmalemma: ergosterol

2. cell wall: chitin (N-acetyl glucosamine polymer)

3. mannans and glucans = polysaccharide capsule

selective for fungi b/c of acid pH and high sugar content

Hypersensitivity pneumonitis

Mycetismus/Mushroom poisoning

Mycotoxin

Caused by inhalation of material contaminated by a variety of molds

acute: 4-8 hrs post-exposure to intermittent high levels --> fevers, chills, cough, SOB

chronic: low level chronic exposure --> insidious onset of cough, SOB, weight loss

acute: 4-8 hrs post-exposure to molds intermittent high levels --> fevers, chills, cough, SOB

chronic: low level chronic exposure to molds --> insidious onset of cough, SOB, weight loss

Farmers lung
Malt-workers lung
Maple bark-strippers lung
Sequoiosis
Suberosis/Cork workers lung
Cheese-washers lung
Ventilator pneumonia (humidifiers, air conditioning)

Most occupational diseases

Type of hypersensitivity pneumonitis

Late winter/early spring when farmers using moldy (Actinomyces) stored hay to feed livestock

Remarkable predominance of non-smokers

Mushroom poisoning

Amanita phalloides (death cap mushroom) causes 95% of North American fatalities

Majority of cases accidentally and in kids

"Death cap" mushroom responsible for 95% North American fatalities from mushroom poisoning.

Primarily in cool coastal regions of West Coast

Alpha-amantin = principle toxin, RNA pol II inhibitor, heat stable and water insoluble (cooking no use)

Triphasic disease

principle toxin of Amanita phalloides, RNA pol II inhibitor, heat stable and water insoluble (cooking no use)

Amanita phalloides poisoning

Ingestion of fungal toxins in foods damaged by molds

e.g. ergot alkaloids, aflatoxins, tricothecene toxin (T-2)

Made by Claviceps purpurea when it infects rye

Converts rye seed into a sclerotium made of fungus

Mycotoxicosis --> alpha adrenergic blockade with peripheral vasoconstriction --> gangrene

aka St. Anthony's fire in Middle Ages

Contaminated feed by Aspergillus fumigatus

Mycotoxicosis = coumarin derivatives produced --> hemorrhages + liver necrosis

Potent liver carcinogen

Present in peanut products

Made by Fusarium sporotrichoides that infects cereal grain left in fields

Causes alimentary toxic aleukia

Manifests as leukopenia + mucositis

Skin (limited to stratum corneum): pityriasis versicolor, tinea nigra

Hair (limited to cuticle): black piedra, white piedra

Fatty acid content of skin

Epithelial turnover

Normal bacterial flora

Malassezia furfur, lipophilic, dimorphic yeast

Dry, scaly, hyperpigmented or hypopigmented lesions on upper torso, arms, abdomen

Rare systemic disease (fungemia) in infants on IV intralipid therapy and peritonitis in patients on chronic ambulatory peritonitis.

Pityriasis versicolor (cutaneous mycosis)

Lipophilic, dimorphic yeast that is part of normal flora, found in areas rich in sebaceous glands

Part of normal flora, found in areas rich in sebaceous glands

Transmitted by direct contact


Increased incidence in tropics, athletes, renal transplant patients, AIDS

KOH prep: classic spaghetti and meatballs (combined yeast and hyphal elements)

Fluoresce yellow under Wood's light (UV lamp)

Tx: selenium sulfide with repeat application to avoid relapse

Depigmented patches may remain for months, esp in winter

Hortae werneckeii, a dimorphic melanin-containing fungus

Flat brown to black macular lesions of palms and soles

Tinea nigra (superficial mycosis)

dimorphic melanin-containing fungus

Found in soil, transmitted by injury

KOH prep: darkly pigmented yeast cells and hyphal fragments

Culture: black colonies

Malassezia furfur: pityriasis versicolor

Piedraia hortae present in perfect state when colonizes hair shaft

Hard, brown to black nodules on infected hair shaft house asci containing ascospores with dark septate hyphae

Black piedra

Microscopic exam of hairs in KOH prep reveals dark pigmented nodules

Trichosporon species, dimorphic fungus

Cream-colored, soft nodules on hair shaft

Can cause disseminated trichosporonosis, mainly in neutropenic and immunocompromised

White piedra

Microscopic exam of hairs in KOH prep reveals white to light brown nodules

Grows on all media except if with cycloheximide. Grows as septate hypae with arthroconidia with septate hyphae

Caused by Trichosporon species and Blastoschizomyces capitatus.

Risk factors = neutropenia + corticosteroids

Sx: fungemia with cutaneous and ocular lesions

Dermatophyte infections usually restricted to skin, hair, nails

Possess keratinases

Differ from superficial mycoses by evoking inflammatory response

Dermatophytes

Tinea pedis

Hyphal form in culture has large club-shaped macroconidia

Fluorescent tinea capitis

In culture, thick walled, spindle-shaped, spiny macroconidia

Trichophyton verrucosum

Inflammatory vesicopustular eruptions, usually unilateral (side toward cow), mistaken for Staph aureus

Tinea barbae

Primarily by Trichophyton tonsurans (does not fluoresce) --endothrix

Also by Microsporum canis (fluoresces) -- ectothrix

Dry, ringlike, scaly, itchy, erythematous lesions in scalp, may present as areas of alopecia (ectothrix)

Spores surround shaft due to destruction of cuticle

May fluoresce or not

Usually presents as areas of alopecia

Gray patches due to hair breaking off just above scalp

spores inside shaft

Trichophyton tonsurans

Hair breaks off at follicle leaving black dot

Kerion: boggy, purulent patches of alopecia, inflammatory

Trichophyton schoenleinii

Thick yellow crust on scalp made of hyphal elements

Hyphae course through the hair shaft with air spaces

Most serious of hair dermatophytes, may lead to alopecia with scarring

Trichophyton rubrum

Scalloped, erythematous, scaling border in groin area (does not involve scrotum)

aka jock itch

Tinea cruris

Onychomycosis

Tinea capitis (non-fluorescent), endothrix

Fluorescent tinea capitis (ectothrix)

Men >> women

Toenails >> fingernails

Prevalence increases with increasing age

Dermatophytes = majority
Trichophyton rubrum
Epidermophyton floccosum
Trichophyton mentagrophytes

Candida

Non-dermatophyte molds (Aspergillus, etc)

Trichophyton rubrum

Classic nail sign of HIV infection

Trichophyton mentagrophytes

HIV

Limited to patients with chronic mucocutaneous candidiasis

psoriasis has sharply defined pitting of nail plate surface

aka Madura foot

subcutaneous mycosis

inoculation due to injury (esp if barefoot)

edema, induration, abscesses, draining sinuses with granules, most commonly of foot

may be bacterial or true fungi (Eumycotic mycetoma)

Nocardia braziliensis if Central/South America (actinomycotic)

Madurella mycetomatis if Africa (eumycotic)

examination of granules (look like miniature colonies)

caused by variety of dermatiaceous fungi (have black/brown pigment in cell wall)

slow development of verrucous (warty) lesions that progress to cauliflower appearance

Chromoblastomycosis

Medlar bodies/sclerotic bodies/copper pennies

Chromoblastomycosis

Sporothrix schenkii, dimorphic

nodular and ulcerative lesions that develop along lymphatics

sphagnum moss, rose thorns, hay bales, cats in Rio de Janeiro, Brazil

Sporotrichosis - Sporothrix schenkii

Sporotrichosis - Sporothrix schenkii

Asteroid bodies aka Splendore-Hoeppli phenomenon

budding cigar-shaped yeast at 37 degrees but delicate hyphae with conidia in rosette pattern at 25 degrees (dx by converting mycelial to yeast phase)

Rhinosporidium seeberi

painless, pedunculated polyps developing in nasal area

Rhinosporidiosis -- Rhinosporidium seeberi

India and Sri Lanka

Loboa loboi (Lacazia loboi)

Keloidal nodules of face, ears, and UL

Lobomycosis -- Loboa loboi (Lacazia loboi)

Histology reveals 10-15 um yeasts in long chains

Caused by dermatiaceous fungi

Disseminated disease in immunocompromised

Histoplasmosis

Inhale conidia (spores) of Histoplasma capsulatum

Calcified granulomas in liver and spleen

Mostly asymptomatic in healthy

Chronic pulmonary and progressive disease in immunocompromised or b/c large inoculum

Ohio and Mississippi River Valleys, Virginia, Maryland, Eastern Seaboard

Bird (starlings, chickens) and bat droppings

Small budding yeast inside macrophage

Histoplasmosis

Histoplasmosis

Older white males with chronic pulmonary disease

Resembles TB

Upper lobe infiltrates on CXR often with cavity formation

Caused by overly exuberant immune response resulting in fibrous proliferation

May progress to constrict airways

Responds poorly to antifungal or surgery

Due to defects in cell-mediated immunity

Acute disseminated: defective T-cell, hematologic malignancies, corticosteroids, AIDS, transplant recipients, infants --> hepatosplenomegaly and pancytopenia

Chronic disseminated: gradual onset of fatigue, weight loss with less organomegaly

Complement fixation

Immunodiffusion

Urine and blood antigen detection by RIA

Direct stains of buffy coat

Delicate septate hyphae with tuberculate macroconidia

Africa

Huge giant cells filled with yeast

Skin lesions = painless, warty dome-shaped papules, may ulcerate, subQ lesions --> cold abscesses

May result in progressive disseminated form (fevers, lymphadenopathy, hepatosplenomegaly)

Inhalation of conidia (spores) of Blastomyces dermatitidis

Symptomatic infection common with pulmonary sx (chest pain, sputum production, fever). Pulmonary infxn may be acute with ARDS with heavy inoculum, self-limited pneumonitis, or chronic disease. Upper lobe alveolar infiltrates. No cavitary lesions.

Progressive disseminated may involve:
skin -- cutaneous lesions are verrucous (warty) or ulcerated

bone -- osteomyelitis

genitourinary tract -- prostatitis,
epididymo-orchitis

CNS -- epidural/intracranial abscesses, chronic meningitis

Blastomycosis

Ohio and Mississippi River Valley, Missouri and Arkansas River basins

Most freq Kentucky, Arkansas, Mississippi, North Carolina, Tennessee, and Louisiana

Also in Wisconsin, Minnesota, Illinois, Virginia (Franklin)

Imp veterinary disease in sporting dogs and horses. Esp raccoon hunters and their dogs.

Assoc w/beaver lodges and canoe trips (outdoor recreation)

Antigen detection test for urine (also BAL, CSF, serum)

ID broad-base budding yeast in tissue biopsy or purulent material or by culture

Culture ID of thermal dimorphism (mold at 25, yeast/pyriform microconidia at 37)

Blastomycosis

Lobomycosis

Paracoccidioides brasiliensis -- dimorphic fungus with multiple buds (pilots wheel)

acute or chronic pneumonia

may disseminate to skin, LN, adrenal glands, spleen, and liver

most typical are oral, nasal, and facial nodular-ulcerative lesions

Central and South America, especially Brazil, Venezuela, Columbia

Males 9x >> females b/c estradiol inhibits mycelia to yeast conversion

Paracoccidioidomycosis

Paracoccidioidomycosis

serologic tests for both yeast and mycelial antigens

KOH prep showing pilots wheel

Culture showing temperature conversion from slow-growing white mold at 25 degrees to pilots wheel yeast at 37 degrees

Coccidioides immitis -- dimorphic, highly infectious in mycelial phase, non-infectious parasitic phase as characterstic spherules

inhalation of arthrospore (highly infectious) -- extremely small inoculation needed

largely asymptomatic

40% clinical pulmonary disease but causes 30% CA-pneumonia in Arizona -- acute pneumonitis, hilar adenopathy, chronic progressive pneumonia, miliary, coccidioma, cavitary disease

Disseminated in 1% but #1 cause of death in Arizona AIDS pts

Primary infection may be assoc w/hypersensitivity rxn (erythema nodosum + arthralgias) = Valley Fever/miners bumps

Coccidioides immitis

disseminated Coccidioides immitis

Southern California, esp San Joaquin Valley, New Mexico, west Texas, Arizona (likes semi-arid climate)

marked increased dissemination in African Americans, Filipinos, pregnancy, immunosuppressed, AIDS in Arizona

coccidioides immitis

Coccidioidomycosis -- Coccidioides immitis

KOH prep shows characteristic spherules

rising eosinophilia

measures delayed hypersensitivity, excellent prognosticator

if positive, means you won't disseminate

if negative, means you probably will disseminate

Disseminated Coccidioidomycosis

Paracoccidioidomycosis

Coccidioidomycosis

hypersensitivity reaction -- erythema nodosum and arthralgias

Coccidioidomycosis

Increasing cause of Candida blood stream infections, esp > 60 y.o.

Intermediate fluconazole resistance b/c drug efflux

May cause breakthrough infections on voraconazole

Use capsofungin

Most common in leukemia patients on fluconazole prophylaxis

Altered CYP450

ALWAYS RESISTANT TO FLUCONAZOLE

amphotericin B resistant, sensitive to azoles

forms extensive biofilms

related to intravascular cathether infections (remove catheter)

involves warm, moist skin folds (intertriginous areas)

erythematous, macerated skin w/vesiculopustular satellite lesions

Candidiasis

predisposition: ABX, steroids, BCP, pregnancy, diabetes

thick, white, vaginal discharge with burning/itching

neonates
recent ABX
denture wearers
inhaled corticosteroids
HIV/AIDS

creamy, curd-like patches

acute atrophic

chronic atrophic (denture wearers)

angular chelitis

Esophageal sx + oral Candida = 90-100% PPV for esophageal disease

Esophageal sx w/o oral Candida = 96% NPV for esophagea disease (is GI issue)

severe chronic cutaneous (skin+nails) and mucosal infxns (lifelong)

specific problem with cell-mediated immunity against Candida

almost never develop systemic/disseminated disease

assoc w/thymomas, hypoparathyroidism, hypoadrenalism, hypothyroidism

some pts have circulating autoantibodies

associated with indwelling bladder catheter

very common, don't treat! usually respond to catheter removal

rarely leads to candidemia

high mortality

often related to central venous catheters, peripherally inserted central catheter -- prompt removal improves outcome

may manifest as failure to thrive w/persistent leukocytosis esp in ICU patients

HIV/AIDS patients, immunocompromised

in patients receiving intensive chemotherapy with profound neutropenia

results in hepatomegaly, elevated alk phos, leukocytosis, multiple nodular densities in liver and spleen on CAT scan

KOH or gram stain demonstrates budding yeast with pseudohyphae

C. albicans ID by formation of germ tubes

Candida species

inhale yeast cells

acute and chronic pneumonia

#1 cause meningitis in AIDS patients (slow onset CNS symptoms that progress to chronic meningitis)

skin lesions often misdiagnosed as molluscum contagiosum

capsular mucopolysaccharide inhibits phagocytosis

pigeon poop

Cryptococcus neoformans

detect polysaccharide antigen by latex agglutination or EIA

India ink prep for rapid dx (fried egg)

mucicarmine stain of tissue (will stain capsule)

brown colonies on bird seed agar

Aspergilloma (fungus ball)

hemoptysis is common sx

in immunocompromised:

allergic bronchopulmonary aspergillosis -- episodic asthma, brown mucous plugs, eosinophilia, elevated IgE

aspergilloma

invasive aspergillosis -- severely immunocompromised, angioinvasive fungus (infarction), rapidly fatal dissemination

invasive aspergillosis

contaminated intravenous arm boards in patients with neutropenia

at site of catheter insertion

progressive ulcers with thick black eschar

biopsy of affected tissue ID septate hyphae with acute angle branching

beta-d-glucan detection assay

caused by Rhizopus, Absidia, and Mucor species

rhinocerebral zygomycosis: most common in diabetics, starts in paranasal sinus and spreads to orbit, hard palate, and brain w/high mortality

pulmonary and cutaneous zygomycoses: immunocompromised, pulmonary lesions/necrotic skin ulcers associated with leukemia, organ transplant, burns

transmitted by inhalation of aerosolized spores

histological examination of tissue ID broad, irregular, non-septate hypahe with wide angle branching, "ribbon-like"

due to molds with hyaline:

Fusarium
Scedosporium
Penicillium
Paecilomyces

Fusarium

may have pre-existing onychomycosis

70% have cutaneous manifestations (cellulitis, target lesions)

may cause sinusitis, rhinocerebral syndrome, endophthalmitis, myositis, and wide dissemination

unlike other fungi, can get (+) blood culture

soft contact lens wearers needing corneal transplants

Scedosporium apiospermium and Scedosporium prolificans

sinusitis, endophthalmitis, pneumonia, and dissemination, esp to CNS

blood cultures (+) with disseminated disease

histopathology like Aspergillus

(all in all, a lot like Fusarium)

resistant to ALL antifungals

3rd most common infection in Thai AIDS, found in SE Asia and China

fever and numerous umbilicated papular skin lesions, hepatomegaly, adenopathy, pneumonia

dx by ID intracellular yeast with clear central septation

Penicillium marneffei

does not have ergosterol

antigenically different between species

primarily alveolar pathogen

ubiquitous, most humans infected before 4 y.o.

cell-mediated immunity plays role in defense

lethal pneumonia of AIDS patients

fever, nonproductive cough, progressive dyspnea on exertion

most common opportunistic infxn in AIDS patients

increased LDH

decreased DLCO, desaturation with exertion

Pythium insidiosum, "water mold"

not a fungus, no chitin, no ergosterol

biflagellate zoospores = infectious form

Thailand -- arterial invasion with arterial insufficiency with thalassemia as risk factor

achlorophyllic algae widely distributed in environment

Prototheca wikerhamii

cutaneous or subQ involvment, often olecranon bursa