Systemic or Endemic Mycoses

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    ENDEMIC MYCOSES/SYSTEMIC

    MYCOSES

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    Outlines General characteristics ofTrue or systemic ( endemic

    mycosis

    Coccidioidomycosis

    Histoplasmosis

    Blastomycosis

    Paracoccidioidomycosis

    Penicillosis

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    SYSTEMIC MYCOSES GENERAL

    CHARACTERISTICS

    Inherently virulent and can cause disease in healthyhumans

    Geographic distribution varies

    Inhalationpulmonary inf. dissemination

    No evidence of transmission among humans or animals

    Causative agents: thermally dimorphic fungi that exist

    in nature, soil

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    SYSTEMIC MYCOSES Contd

    Most infections are asymptomatic or self-limiting

    In immune-compromised hosts, infections are more

    often fatal

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    COCCIDIOIDOMYCOSIS

    Etio:Coccidioides immitis/posadasiiLocation: Confined to south-western

    US, Northern Mexico, Central

    and South America

    Micr: Tissue(37C):Spherules filled with endospores

    25C: hyphae, barrel-shaped arthroconidia

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    COCCIDIOIDOMYCOSISPathogenesis

    Grows in the soil, but inhalation of a single spore caninitiate infection.

    Inhalation of the infectious particle, arthroconidia andspherule formation in vivo

    Engulfment within phagosomes by alveolar MQs

    Activation of macrophages ---phagosome-lysosomefusion ---killing

    Immune complex formation

    deposition leading to local inflammatory rx.s

    immunosupression resulting from the binding ofcomplexes to cells bearing Fc receptors

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    COCCIDIOIDOMYCOSIS contd

    Clinical manifestation

    Primary infectionAsymptomatic in most cases

    The most common symptoms include cough, fever, chest pain,headache, fatigue, chills, malaise, and anorexia

    Nodular lesions in lungs

    Cutaneous infection acquired via a percutaneous route

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    COCCIDIOIDOMYCOSIS contd

    Secondary (disseminated) inf. (1%)

    Chronic / fulminant

    Infection of lungs, meninges, bones, jointsubcutaneous and cutaneous tissues

    Lesions in the skin and subcutaneous tissues

    occur in more than 65% of cases

    May present as small papular nodules, ulcerated

    nodules, or verrucous granuloma

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    Chronic cutaneous coccidioidomycosis

    showing granulomatous lesions of the face,

    neck and chin

    Extension of pulmonary coccidioidomycosisshowing a large superficial, ulcerated plaque

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    COCCIDIOIDOMYCOSISDiagnosisSamples

    Skin scrapingsSputum and bronchial washings,

    Cerebrospinal fluid, pleural fluid and blood,

    Bone marrow, urine

    Tissue biopsies from various visceral organsDirect examination

    Skin scrapings using 10% KOH and Parker ink or calcofluorwhite mounts

    Exudates and body fluids should be centrifuged and the sedimentexamined using either 10% KOH and Parker ink or calcofluorwhite mounts

    Tissue sections should be stained using Periodic acid-Schiff (PAS),

    Grocott's methenamine silver (GMS) or Gram stain, H&E

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    COCCIDIOIDOMYCOSIS contd

    Culture

    SDA: Mould colonies at 25 C

    Spherule production in vitro by incubation in an

    enriched medium at 40C, 20% CO2

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    cutaneous lesion mounted

    in 10% KOH and Parker ink Culture ofCoccidioides immitis showing a

    suede-like todowny, greyish white colony

    with a tan to brown reverse

    Tissue section showing typical

    endosporulating spherules of

    Coccidioides immitis

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    COCCIDIOIDOMYCOSIS contd

    3. Serology

    Tube precipitin (IgM) test

    Complement fixation

    Skin test (coccidioidin and spheruline antigens)

    Negative result may rule out the diagnosis

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    COCCIDIOIDOMYCOSIS contd

    Treatment

    Symptomatic treatment only (primary infection)

    Amphotericin B Itraconazole

    Fluconazole (particularly for meningitis)

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    HISTOPLASMOSIS

    Histoplasmosis is an intracellular mycotic

    infection of the reticuloendothelial system

    Etio:Histoplasma capsulatum

    Natural reservoir:soil, bat and avian habitats

    Location:May be prevalent all

    over the world

    But the incidence varies widely

    (most endemic in Ohio,Mississipi,

    Kentucky)

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    HISTOPLASMOSIS contd

    Micr.

    Yeast cell in tissue (37C)

    Hyphae, microconidia and macroconidia

    (tuberculate chlamydospore) at 25 C

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    HISTOPLASMOSIS contd

    Pathogenesis

    Inhalation of microconidia / primary cutaneous

    inoculation

    Conversion to budding yeast cells

    Phagocytosis by alveolar macrophages

    Restriction of growth or dissemination to RES bybloodstream

    Supression of cell-mediated immunity

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    HISTOPLASMOSIS contd

    Clinical Manifestation

    PULMONARY INF.

    Asymptomatic (%95) / mild / moderate / severe/ chronic

    cavitary

    DISSEMINATED INF.

    RES (liver, spleen, lymph nodes, bone marrow),

    mucocutaneous inf.PRIMARY CUTANEOUS INF.

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    Histoplasmosis of the lower gum showing

    ulcer around base of the teeth

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    HISTOPLASMOSIS contd

    DiagnosisSamples:Sputum, tissue, bone marrow, CSF, blood

    1. Direct examination:Giemsa / Wright

    Intra- and extracellular yeast cells

    Inside the macrophages and polymorphonuclear

    leukocytes

    2. Culture:Mould at 25C

    Conversion to yeast on an enriched medium at 37C

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    HISTOPLASMOSIScontd

    3. Serology:Complement fixation...

    Skin test (Histoplasmin antigen):

    Limited diagnostic value

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    AFRICAN HISTOPLASMOSIS

    Etio:Histoplasma capsulatum var. duboisii

    Differentiation from classical histoplasmosis

    Larger, thick-walled yeast cells

    Pronounced giant cell formation in infected tissue

    Diminished pulmonary involvement

    Greater frequency of skin and bone lesions

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    Tissue morphology ofH. capsulatum var. capsulatum (left) showing

    numerous small narrow base budding yeast cells (1-5m diam)

    inside macrophages

    H. capsulatum var. duboisii(right) showinglarger sized budding yeast cells (5-12 m in diam).

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    HISTOPLASMOSIS contd

    TreatmentNot required for several cases

    Amphotericin B

    Itraconazole

    Surgical resection of pulmonary lesions

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    BLASTOMYCOSIS

    Granulomatous mycotic infection

    Predominantly involves lungs and skin

    can spread to other organs

    Most prevalent in males 40-60 years of age and

    children.

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    BLASTOMYCOSIS contd

    Etio:Blastomyces dermatitidis

    Location:America, Africa, Asia

    Micr.:

    Yeasts at 37C--bud is attached to

    the parent cell by a broad base

    Hyphae and conidia at 25 C

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    BLASTOMYCOSIS

    Pathogenesis

    Inhalation of infectious particles

    Primary cutaneous inoculation

    Infiltration of macrophages and neutrophils and

    granuloma formation

    Oxidative killing mechanisms of neutrophils and

    fungicidal activity of macrophages

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    BLASTOMYCOSIS

    Clinical manifestation Asymptomatic inf.

    Pulmonary inf.

    Chronic cutaneous inf.

    Subcutaneous nodule, ulceration

    Disseminated inf.

    Skin, bone, GUT, CNS, spleen

    Primary cutaneous inf.

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    BLASTOMYCOSIS Contd

    Pulmonary blastomycosis

    In most individuals pulmonary lesions asymptomatic notdetecteduntil the infection has spread to other organs

    Indolent in onset and patients present with chronicsymptoms suchas cough, fever, malaise and weight loss

    Lesions become more extensive, with continuedsuppuration and eventual necrosis and cavitation

    Occasional an acute onset of infection, with development of high fever, chills, productive cough,

    myalgia, arthralgia and pleuritic chest pain

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    BLASTOMYCOSIS Contd

    Ulcerated granuloma due to

    B. dermatitidis

    Cutaneous blastomycosis

    Haematogenous spread gives rise to

    cutaneous lesions in over 70% of patients

    Lesion tend to be painless and present

    either as raised verrucous lesions with

    irregular borders, or as ulcers

    The face, upper limbs, neck and scalp

    are the most frequent sites involved.

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    BLASTOMYCOSIS Contd

    Diagnosis

    Samples:Sputum, tissue

    1. Direct micr. exam:KOH, H&E

    Yeast cells; bud is attached to

    the parent cell by abroad base

    2. Culture:Mould at 25C

    Conversion to yeast on an enriched medium at 37C

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    BLASTOMYCOSIS

    Diagnosis

    3. Serology:Immunodiffusion test

    ELISA to detect antibodies to exoantigen A

    Skin test (Blastomycin antigen)

    Limited/no diagnostic value

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    BLASTOMYCOSIScontd

    Treatment

    Amphotericin B

    Itraconazole

    Fluconazole

    Corrective surgery

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    PARACOCCIDIOIDOMYCOSIS

    Etio:Paracoccidioides brasiliensis

    Micr.: At 37C (in tissue ): multiply budding yeasts; the buds are attached to the

    parent cell by a narrow base At 25 C: hyphae and conidia

    Location:

    Central and South America

    The disease is more

    common in warm and moist

    climates

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    PARACOCCIDIOIDOMYCOSIS contd

    Pathogenesis: Inhalation of conidia

    Determinants of pathogenicity

    Has a protein in its cytoplasm which binds only toestrogen but not to testosterone

    The inf. is more common in males

    Yeast cell wall polysaccharides (alpha-glucan) stimulategranuloma formation

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    PARACOCCIDIOIDOMYCOSIS contd

    Clinical manifestation Asymptomatic inf.

    Latent form (duration variable)

    Symptomatic inf.

    Noduler lesions in lungs

    Dissemination to other organs (rare)

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    PARACOCCIDIOIDOMYCOSIS contd

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    PARACOCCIDIOIDOMYCOSIS contd

    Diagnosis-

    Samples: Sputum, tissue

    1. Direct micr exam.:KOH, H&E Multiply budding yeasts;

    The buds are attached to the parent cell by a narrow

    base

    2. Culture:

    Mould at 25C

    Conversion to yeast on an enriched medium at 37C

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    PARACOCCIDIOIDOMYCOSIS contd

    3. Serology:Immunodiffusion

    Complement fixation

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    PARACOCCIDIOIDOMYCOSIS Contd

    Treatment

    Amphotericin B

    Ketoconazole

    Itraconazole

    Sulfonamides

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    Penicillosis

    Important OIs in AIDS patients in in south east

    Asia, Thailand

    Etio. Penici l l ium marneffei

    Location : South east Asia

    Thailand

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    Penicillosis Contd

    Reservoir: bamboo rat

    Endemic season: rainy season

    Route of infection: inhalation

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    Penicillosis Contd

    Clinical manifestation

    Symptoms: fever, chill, cough, chest pain, weight

    loss

    Lesion the lung, skin lesions (face, arm, neck, torso

    Disseminated infection (more frequent)

    Hepatomegaly, lymphadenopathy, lesion

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    Penicillosis Contd

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    Penicillosis Contd

    Diagnosis

    A Giemsa stained touch smear of a skin biopsy or bone

    marrow aspirate is a rapid and sensitive diagnostic

    Histopathologic exam and culture of skin, lymph node,bone marrow

    Demonstrates the presence of typical

    yeast-like cells with a central septa

    Yeast-cells are spherical to ellipsoidal

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    Penicillosis Contd

    Treatment

    Amphotericin B

    Itraconazole

    Secondary prophylaxis in AIDS

    Itraconazole