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57 Cards in this Set

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Anti-fungal targets

Ergosterol: principal sterol


-Amphotericin: binds to ergesterol


-Azole antifungal drugs: inhibits enzyme that makes ergosterol


Cell wall complex carb components (complex carbs including chitin with glucans and mannose-proteins)

Fungal infection epidemiology

-neglected worldwide


-infections "hidden" bc of other health problems


-300 million serious infections/yr (most: skin/mucosa; easy to treat. Invasive/chronic: hard to treat)


-1.5-2 million deaths/yr (~TB and malaria)


-eyesight loss from fungal keratitis (farming)

Candidiasis

-Candida albicans


-most common worldwide infection


-UNIQUE: apart of normal flora

Fungi classification/characteristics

-Eukaryotes


-cell wall of complex carbs: chitin, glucans and mannose-proteins) (Anti-fungal therapies)


-5-20% chitin



Yeast morphology

-Colonial: similar to bacterial colony morphology and disease spectrum


-Microscopic: pseudohyphae, budding

Mold morphology

-Colonial: fluffy, airborne filaments


-Microscopic: hyphae or mycelia (branching hyphae), mycelia branching, spore case

Dimorphic Fungi

-grow as mold in cold


-grow as yeast in heat

Fungal disease diagnosis

1. Staining: direct tissue examination


-Histo stains: silver stains


-Wet mount: 10% KOH


2. Culture: (e.g. Sabouraud agar)


-colonial morphology- vegetative vs reproductive


-temp requirements: dimorphic


3. Serology: detects Ab


4. Skin test


5. Nucleic acid amplification (i.e. PCR)

Mycoses def

Diseases caused by Fungi

Fungal Virulence Factors

1. Invasion and destruction of tissue and/or


2. Obstruction of flow of bodily fluids or by their toxins

Fungal Virulence Factors 2

-cell walls attach to host


-direct hyphal invasion of tissue


-tissue reactive enzymes: protease, keratinase, elastase


-capsule


-inhibit complement


-toxins: amatoxins from mushrooms, aflatoxins from aspergillus

Amatoxin

toxin in mushroom

Aflatoxin

toxin in aspergillus


grows on peanuts

Innate immunity factors against fungi

-high


-most infections mild, self-limiting


-resistance mechanisms: fatty acid on skin, pH, epithelial cell turnover, normal flora, transferrin, cilia in respiratory tract (cough out)

Mycoses divided by where they cause problems

-Superficial


-Subcutaneous (papillary dermis)


-Cutaneous (reticular dermis)


-Deep Systemic


-Opportunistic

Superficial Mycoses


-locations


-infections

-Outer skin, hair, hair shafts, epidermis


-Black piedra: scalp hair, eyebrows, eyelashes


-White piedra: mustache, beard, pubic, axilla hair


-Ringworm (Tinea): 1. Tinea Versicolor: chest, back. 2. Tinea nigra: palms

Black Piedra

-rare


-superficial mycoses


-scalp hair, eyebrows, eyelashes


-Piedra hortae

White Piedra

-common


-superficial mycoses


-mustache, beard, pubic, axilla hair


-Trichosporon beigelii



Tinea vericolor

-common


-superficial mycoses


-ringworm of chest, back


-Malassezia furfur

Tinea nigra

-rare


-superficial mycoses


-ringworm of palms


-Hortaea werneckii

Spread of Superficial mycoses

-skin to skin


-animal to human (animals are major carriers of dermatophytes)


-contact with infected obj (fomite) like towels, linens


-infected soil contact (less common)

Dermatophytes

-Animals are carriers

Cutaneous Mycoses


-caused by...


-infection location


-3 primary species

-dermatophytes


-living layer of skin, hair shaft, nails


-Microsporum, Trichophyton, Epidermophyton

Tinea meaning

-fungal infection AKA ringworm


-NOT caused by worm

Tinea of Cutaneous skin


"Tinea"...


-c


-p


-u


-c


-m


-c

-cruris (jock itch)


-pedis (athletes foot)


-unguium (nail)


-capitis (head)


-manus (hand)


-corporis (body)

Jock itch

-Tinea cruris

Athlete's foot

-Tinea pedis

Nail fungus

-Tinea unguium

Head Fungus

-Tinea capitis

Hand Fungus

-Tinea Manus

Body fungus

-Tinea corporis

Treatment of Cutaneous Fungal Infections


-easy, but long treatment; can resurface

-Imidazoles

-Allylamines


-Naphthiomates


-Substituted pyridines



Subcutaneous Mycoses

-dermis, subcutaneous tissues, muscle, fascia


-initiated by trauma to skin (e.g. poked with plant)


-hard to treat


-often surgical intervention (amputation)

Systemic Mycoses


1. originate where?


2. spread where and cause what?


3. common causes (3)

-most serious fungal infections


1. lungs


2. other organs; if CNS, causes fungal meningitis


3. dimorphic species:


-Blastomyces dermatiditis


-Histoplasma capsulatum


-Coccidiodes immitis

-Blastomyces dermatiditis


-Histoplasma capsulatum


-Coccidiodes immitis



-Dimorphic fungal species that commonly cause systemic mycoses

Coccidiomycosis (Valley Fever)


1. Type of mycosis


2. dimorphic


3. Spores-name, location, route of infection


4. Primary infection


5. Diagnosis


6. Major risk factor


7. CDC reporting

1. systemic mycosis


2. mold at room temp, yeast at body temp


3. Arthrospores, soil in arid western hemisp (SW US, Mexico), inhaled and engulfed by macrophages but not killed


4. asymptomatic or self-limited; may disseminate yrs later and cause chronic infection


5. Sputum, cultures, chest x-ray, blood test


6. AIDS


7. ONLY Fungal disease that must be reported to CDC

Histoplasma capsulatum


1. Type of mycosis


2. dimorphic


3. Primary lesion location


4. Symptoms


5. Risk factor


6. Reservoir


7. Transmission


8. Exposure stats


9. Rare serious cases

1. Systemic mycosis


2. Mold in cold, yeast in heat


3. Lungs


4. Fever, chills, myalgia, nonproductive cough, chest pain


5. ANYONE, not just immunocompromised


6. Warm moist soil, esp with bat or bird poo in it


7. inhalation of asexual spores (conidia)


8. 80% of people in Midwest and Southern US; 10-25% of AIDS pt's in this area will get infection


9. Can cause blindness, joint pain, meningitis, heart problems

Presumed Ocular Histoplasmosis

-even mild cases of histoplasma can later cause this


-tiny fraction of those infected with histoplasmosis develop POHS


-a leading cause of vision loss in Americans aged 20-40


-"Histo spots": small areas of inflammation and scarring of retina.


-Most unaware until central vision affected


-Vision loss secondary to macular choroidal neovascularization

Opportunistic Mycoses seen in...

-people with impaired host defenses: AIDS, alteration of normal flora, DM, immunosuppressive therapy, malignancy

Opportunistic Mycoses


-most common fungi that cause

-Candida albicans


-Cryptococcus neoformans


-Aspergillus species


-Pneumocystis jiroveci

Candida albicans

-opportunistic infection


-normal flora of oropharynx and female GU tract


-a leading cause of nosocomial bloodstream infection


-most common isolated yeast from clinical specimens


-causes thrush, vaginitis, and fungal endocarditis


-mainly seen in immunocompromised

Cryptococcus neoformans


1. Infection type


2. Virulence


3. Infection spread


4. Diagnosis


5. Transmission


6. Risk factor

1. Opportunistic infection


2. yeast with CHO capsule


3. Lung to brain--> meningitis


4. CSF


5. Inhalation of soil with bird poo


6. commonly seen in AIDS pts

Pulmonary Aspergillosis

-Opportunistic infection


-inhalation of spores


-high mortality


-often confused with TB

Pneumocystis jirovecii

-opportunistic respiratory pathogen


-AIDS-defining disease


-transmission by aerosol


-can't be cultured

Exserohilum

-Caused meningitis outbreak in epidurals


-common mold in soil, plants. In warm, humid climates


-Common infections: sinusitis, skin infections.


-Also causes keratitis, endocarditis, and osteomyelitis



Fungal Meningitis Symptoms

-New or worsening HA


-Fever


-Light sensitivity


-Stiff neck


-New weakness/numbness in any body part


-Slurred speech


-Increased pain, redness or swelling at injection site

Fungal infection treatment

-Drug development stalled in 1990s


-Drugs only have modest success in reducing mortality rates due to lack of early diagnosis and fungal identification


-Drugs limited in route of administration, spectrum of activity, and bioavailability


-Other drug problems: toxic, interactions, resistance, cost


-NO vaccines for any fungal pathogens

House Molds

-exposure linked to: upper respiratory tract symptoms, asthma symptoms in those with asthma, hypersensitivity pneumonitis


-wet cellulose materials support mold growth


-Mold removal: cleaning commercial products, soap and water, 1 cup bleach + 1 gallon water


-Mold growth indicates underlying problem with water or moisture

Fungal Eye Infections

-common (1 million/yr)

Causes of one-third of cases of traumatic infectious keratitis

Filamentous fungi such as Fusarium solani and Aspergillus flavus

Endogenous Fungal endophthalmitis (4 species)

-systemic fungal infection that spreads to eye


-most common causes: Candida species, Aspergillus


-Cryptococcus: spores survive for 2yrs in pigeon poo


-Coccidioides immitis: inhalation of arthroconidia in dust of endemic areas can spread to the eye hematogenously



Exogenous Fungal endophthalmitis (3 species)

-secondary to trauma/surgery


-Paecilomyces, Acremonium, Sporothrix

Mycotic Keratitis

-corneal infection by mold or yeast


-risk factors: trauma (w plant material), chronic ocular surface disease, c.l use, surgery, corneal anesthetic abuse, immunodeficiencies


-related to warm climates


-South states: 35% of microbial keratitis


-NY: 1% of microbial keratitis

Challenge of Mycotic Keratitis

-limited drugs available (Natacyn)


-drugs must be used often


-oral antifungals also needed bc fungal ulcers too deep


-treatment that kills the fungi also produces great inflammatory reaction in cornea


-treatment could last months

Ocular Candidiasis (Candida endophthalmitis)

-associated with candidemia, catheters, IV drug use (most common)


-rare in patients with neutropenia


-macular lesions


-symptoms: cloudy vision, red eye, photophobia, pain, floaters, scotoma


-most caused endogenously; exogenous infection rare

Diagnosis of endogenous fungal endophthalmitis

-pts presenting with vitritis accompanied by chorioretinal focus


-Blood, urine, sputum, and CSF cultures should be taken


-Direct examination of fungi should be obtained


-PCR: useful diagnostic tool


-DNA microarray: used for rapid diagnosis

Fungal (Fusarium) Keratitis associated with c.l. wear

-Filamentous fungus


-soil, water, organic matter


-difficult to treat