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    Fungi as Infectious Agents

    Molds and yeasts are widely distributed in air,dust, fomites and normal flora.

    Humans are relatively resistant.

    Fungi are relatively nonpathogenic. Of the 100,000 fungal species, only 300 have been

    linked to disease in animals.

    Fungi are the most common plant pathogens.

    Human mycosesare caused by true fungalpathogens and opportunistic pathogens.

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    Trueor primaryfungal pathogen can invade

    and grow in a healthy, noncompromised host.

    Most striking adaptation to survival and

    growth in the human host is the ability to

    switch from hyphal cells to yeast cells.

    Thermal dimorphismgrow as molds at30C and as yeasts at 37C

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    Emerging Fungal Pathogens

    Opportunistic fungal pathogen has little or novirulence; host defenses must be impaired.

    Vary from superficial and colonization to

    potentially fatal systemic disease An emerging medical concern; account for

    10% of all nosocomial infections

    Dermatophytes may be undergoingtransformation into true pathogens.

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    Epidemiology of the Mycoses

    Most fungal pathogens do not require a host tocomplete their life cycles and infections are notcommunicable.

    Dermaphytes and Candida spnaturally inhabit

    human body and are transmissible. True fungal pathogens are distributed in a

    predictable geographical pattern - climate, soil.

    Dermaphytoses most prevalent

    Cases go undiagnosed or misdiagnosed. Systemic, subcutaneous, cutaneous or superficial

    infections

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    Pathogenesis of the Fungi

    Portal of entryprimary mycosesrespiratory portal; inhaled

    spores

    subcutaneous - inoculated skin; trauma

    cutaneous and superficialcontamination ofskin surface

    Virulence factorsthermal dimorphism,

    toxin production, capsules and adhesionfactors, hydrolytic enzymes, inflammatorystimulants

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    Antifungal defenses are the integrity of thebarriers and respiratory cilia.

    Most important defenses are cell-mediated

    immunity, phagocytosis, and inflammation. Long-term immunity can only develop for

    some.

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    Diagnosis of Mycotic Infections

    Diagnosis and identification requiremicroscopic examination of stained specimens,

    culturing in selective and enriched media and

    specific biochemical and serological tests.

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    Control of Mycotic Infections

    Immunization is not usually effective.

    Control involves intravenous amphotericin B,

    flucytosine, azoles and nystatin.

    In some cases surgical removal of damaged

    tissues

    Prevention limited to masks and protective

    clothing to reduce contact with spores

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    Systemic Infections by True Pathogens

    Deep Mycosis/ Systemic Mycosis

    Histoplasma capsulatum

    Coccidioides immitis

    Blastomyces dermatitidis

    Paracoccidioidesbrasiliensis

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    Histoplasmosis: Ohio Valley Fever

    Histoplasma capsulatum

    most common true

    pathogen; causes histoplasmosis

    Typically dimorphic

    Distributed worldwide, most prevalent in eastern andcentral regions of US

    Grows in moist soil high in nitrogen content

    Inhaled conidia produce primary pulmonary infectionthat may progress to systemic involvement of a variety

    of organs and chronic lung disease.

    Amphotericin B, ketoconazole

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    Coccidioidomycosis: Valley Fever

    Coccidioides immitis - causes coccidioidomycosis

    Distinctive morphologyblocklike arthroconidia

    in the free-living stage and spherules containing

    endospores in the lungs

    Lives in alkaline soils in semiarid, hot climates

    and is endemic to southwestern U.S.

    Arthrospores inhaled from dust, creates spherules

    and nodules in the lungs

    Amphotericin B treatment

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    Blastomyces dermatitidis: North

    American Blastomycosis

    Blastomyces dermatitidis- causes blastomycosis

    Dimorphic

    Free-living species distributed in soil of a large

    section of the midwestern and southeastern U.S. Inhaled 10-100 conidia convert to yeasts and

    multiply in lungs

    Symptoms include cough and fever.

    Chronic cutaneous, bone, and nervous systemcomplications

    Amphotericin B

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    Paracoccidioidomycosis

    Paracoccidioidesbrasiliensis

    Distributed in Central and South America

    Lung infection occurs through inhalation or

    inoculation of spores.

    Systemic disease is not common.

    Ketoconazole, amphotericin B, sulfa drugs

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    Insert figure 22.13

    Paracoccidioides morphology

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    Subcutaneous Mycoses

    Lymphocutaneous sporotrichosis

    Chromoblastomycosis

    Mycetoma

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    Chromoblastomycosis

    A progressive subcutaneous mycosischaracterized by highly visible verrucous

    lesions

    Etiologic agents are soil saprobes with dark-pigmented mycelia and spores

    Fonsecaea pedrosoi, Phialophora verrucosa,

    Cladosporium carrionii Produce very large, thick, yeastlike bodies,

    sclerotic cells

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    Mycetoma

    When soil microbes are accidentallyimplanted into the skin

    Progressive, tumorlike disease of the hand

    or foot due to chronic fungal infection; maylead to loss of body part

    Caused byPseudallescheriaorMadurella

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    Opportunistic Mycoses

    Most important fungal pathogens:Aspergillus

    Candida

    CryptococcusPneumocystis

    Rhizopus

    Mucor

    Absidia

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    Infections by Candida: Candidiasis

    Candida albicans

    Widespread yeast

    Infections can be short-lived, superficial skin

    irritations to overwhelming, fatal systemicdiseases.

    Budding cells of varying size that may form both

    elongate pseudohyphae and true hyphae

    Forms off-white, pasty colony with a yeasty odor

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    Candida albicans

    Normal flora of oral cavity, genitalia, large intestine orskin of 20% of humans

    Account for 80% of nosocomial fungal infections

    Account for 30% of deaths from nosocomial infections

    Thrushoccurs as a thick, white, adherent growth onthe mucous membranes of mouth and throat

    Vulvovaginal yeast infectionpainful inflammatorycondition of the female genital region that causesulceration and whitish discharge

    Cutaneous candidiasisoccurs in chronically moistareas of skin and in burn patients

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    Diagnosis and Treatment

    Presumptive diagnosis made if buddingyeast cells and pseudohyphae are found;germ tube

    Growth on selective, differential mediadifferentiates Candida species

    Topical antifungals for superficialinfections, amphotericin B and fluconazole

    for systemics

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    Cryptococcosis and Cryptococcus

    neoformans

    Cryptococcus neoformanscauses cryptococcosis.

    A widespread encapsulated yeast that inhabits soil

    around pigeon roosts

    Common infection of AIDS, cancer or diabetes

    patients

    Infection of lungs leads to cough, fever, and lung

    nodules Dissemination to meninges and brain can cause severe

    neurological disturbance and death.

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    Diagnosis and Treatment

    Negative stain demonstrating encapsulated

    budding yeast

    Biochemical tests, serological testing

    Systemic infection requires amphotericin B

    and fluconazole.

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    Pneumocystis (carinii) jiroveciand

    Pneumocystis Pneumonia

    A small, unicellular fungus that causespneumonia (PCP), the most prominentopportunistic infection in AIDS patients

    This pneumonia forms secretions in thelungs that block breathing and can berapidly fatal if not controlled with

    medication. Pentamidine and cotrimoxazole

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    Aspergillosis: Diseases of the Genus

    Aspergillus

    Very common airborne soil fungus

    600 species, 8 involved in human disease;A. fumigatusmost commonly

    Serious opportunistic threat to AIDS, leukemia, andtransplant patients

    Infection usually occurs in lungsspores germinate inlungs and form fungal balls; can colonize sinuses, ear

    canals, eyelids, and conjunctiva Invasive aspergillosis can produce necrotic pneumonia,

    and infection of brain, heart, and other organs.

    Amphotericin B and nystatin

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    Zygomycosis

    Zygomycota are extremely abundant saprobic fungifound in soil, water, organic debris, and food.

    Genera most often involved areRhizopus, Absidia,

    and Mucor.

    Usually harmless air contaminants invade the

    membranes of the nose, eyes, heart, and brain of

    people with diabetes and malnutrition, with severe

    consequences.

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    Miscellaneous Opportunists

    Any fungus can be implicated in infectionswhen immune defenses are severelycompromised.

    Geotrichum candidumgeotrichosis; moldfound in soil, dairy products; primarilyinvolved in secondary lung infections

    Fusarium speciessoil; occasionallyinfects eyes, toenails, burned skin

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    Fungal Allergies and Intoxications

    Fungal spores are common sources of atopic allergies. Seasonal allergies and asthma

    farmers lung, teapickers lung, bark strippers

    disease

    Fungal toxins lead to mycotoxicosesusually caused by

    eating poisonous or hallucinogenic mushrooms.

    aflatoxintoxic and carcinogenic; grains, corn

    peanuts; lethal to poultry and livestock Stachybotrys chartarumsick building syndrome;

    severe hematologic and neurological damage