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    Systemic Mycosis 06-07

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    1) The patient presented with respiratory failure, altered mental status, and meningitis. Examination of CSF by calcofluor stain revealed encapsulated budding yeast, consistent with Cryptococcus. 2) Risk factors included immunosuppression from steroids and poorly controlled diabetes. 3) Despite antifungal therapy, the patient deteriorated rapidly, as disseminated cryptococcosis has a high mortality rate in immunocompromised individuals.

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    Systemic Mycosis 06-07

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    351 views41 pages
    1) The patient presented with respiratory failure, altered mental status, and meningitis. Examination of CSF by calcofluor stain revealed encapsulated budding yeast, consistent with Cryptococcus. 2) Risk factors included immunosuppression from steroids and poorly controlled diabetes. 3) Despite antifungal therapy, the patient deteriorated rapidly, as disseminated cryptococcosis has a high mortality rate in immunocompromised individuals.

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    1) The patient presented with respiratory failure, altered mental status, and meningitis. Examination of CSF by calcofluor stain revealed encapsulated budding yeast, consistent with Cryptococcus. 2) Risk factors included immunosuppression from steroids and poorly controlled diabetes. 3) Despite antifungal therapy, the patient deteriorated rapidly, as disseminated cryptococcosis has a high mortality rate in immunocompromised individuals.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    351 views41 pages

    Systemic Mycosis 06-07

    Uploaded by

    api-3699361
    1) The patient presented with respiratory failure, altered mental status, and meningitis. Examination of CSF by calcofluor stain revealed encapsulated budding yeast, consistent with Cryptococcus. 2) Risk factors included immunosuppression from steroids and poorly controlled diabetes. 3) Despite antifungal therapy, the patient deteriorated rapidly, as disseminated cryptococcosis has a high mortality rate in immunocompromised individuals.

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    Download as ppt, pdf, or txt
    of 41

    Systemic Mycoses

    Caustive agents
     Histoplasma capsulatum
     Blastomyces dermatitidis
     Cryptococcus neoformans
     Coccidioides immitis
     Paracoccidioides brasillensis
    Histoplasmosis
    Causative Agent
    Histoplasma capsulatum var capsulatum
    Histoplasma capsulatum var. duboisii
    o The organism is misnamed because:
     It infects macrophages NOT plasma cells &
     It is non-capsulated
    Morphology
     Dimorphic fungus
     Smallest yeast cells
     Reproduce by budding
    Histoplasmosis

    Source of Infection
    • Soil containing bird or bat excreta
    • No case to case transmission
    Pathogenesis
    • Spores are inhaled, engulfed by
    macrophages and develop into yeast
    forms Histoplasma yeasts
    • Granulomas formed in the lung which within macrophages

    may get calcified like TB


    • Disseminate and may infect
    macrophages in RES (liver, spleen,
    LN & BM)
    Histoplasmosis
    Clinical Features

    • In immunocompetent persons
    o Asymptomatic or flue-like symptoms
    o Chronic lesions in lungs give TB-like picture

    • In immunosuppressed persons
    o Disseminated infection
    o Febrile illness
    o Enlargement of RE system, hepatosplenomagaly
    o Ulcerated lesions on tongue in AIDS patients
    Histoplasmosis
    Lab Diagnosis
    • Direct examination of sputum
    • Not helpful as few organisms in sputum
    • Bone marrow aspirate histology :
    • Oval yeast cells within macrophages by Giemsa stain
    • Culture on Sabouraud’s Dextrose Agar incubate at
    25oC & 37oC to show dimorphic forms
    • Serology
    o An Ab titre of 1:32 with yeast phase Ags is
    considered diagnostic
    • Histoplasmin skin test: Epidemiological value only
    • Histopathology of BMA: to see parasitic yeast form
    Oral lesions following hematogenous
    dissemination
    Macroconidia and microconidia. Phase contrast
    .
    microscopy, potato glucose agar, slide culture, 25C
    Rough-walled macroconidia, Sabouraurd glucose
    agar, 25C, lactophenol cotton blue preparation.
    Yeast form growing at 37C in the laboratory.
    Phase contrast microscopy, 37C, 630X
    Histoplasmosis

    Treatment
    • Oral itraconazole

    • Disseminated disease
    o Amphotericin B
    o Fluconazole in meningitis
    • May need surgical resection of pulmonary lesions
    BLASTOMYCOSIS
    Pathogenesis
    • Blastomyces dermatitidis
    • Dimorphic fungus
    Pathogenesis
    • Inhalation of infectious particles
    • Cutaneous inoculation
    • Infiltration of macrophages and neutrophils
    and granuloma formation
    BLASTOMYCOSIS
    Clinical findings
    • Asymptomatic
    • Pulmonary infection
    • Chronic skin infection
    • Subcutaneous nodule & ulceration
    • Disseminated infection
    • Bone, GUT, CNS, spleen
    Broad based budding and thickened
    Broad based budding yeast cell walls and globose shape are
    characteristic of the yeast form of
    cells, KOH, from a lung
    Blastomyces dermatitidis.
    Colony of Blastomyces dermatitidis on Mold
    Inhibitory Agar after14 days, 30C.
    Skin lesion following dissemination from the lungs.
    The cutaneous lesion developed following
    dissemination of the fungus from the lungs.
    Treatment
    • Amphotericin B
    • Azoles are alternative in immuocompetent
    patients
    Cryptococcosis

    Causative agent
    India Ink Preparation

    Cryptococcus neoformans (5µ)


    o A typical yeast with a thick capsule
    (25µ)
    o Urease positive
    Source of infection
    • Pigeon or birds droppings &
    contaminated soil
    Cryptococcosis

    Pathogenesis
    • Capsule is the virulence factor (antiphagocytic)

    • Human infection by inhalation

    • Most infections are asymptomatic

    • May develop pneumonia

    • Disseminate to CNS causing meningitis


    Cryptococcosis

    Clinical Features
    • Disease usually affects immunocompromised
    • Lung infection usually asymptomatic
    • Cryptococcal meningitis
    o Among top four life-threatening infections in AIDS
    Meningitis
    • Intermittent headache & dizziness & vomiting
    • Difficulty in thinking
    • Slight fever
    • Slowly progressing to weight loss, impairment of
    nerves
    • May be difficult to diagnose in early stages
    Cryptococcosis

    Lab Diagnosis
    • CSF Examination
    India Ink Preparation
    o Turbid CSF
    o Decreased glucose & increased protein
    o Increased cell count >100 cells mostly
    lymphocytes
    o India Ink preparation
     Yeast cell with a thick capsule
    o Periodic acid-Schiff (PAS), detect
    fungal elements
    o Culture on SDA (grows in 48-72 hrs)
    o Capsular Antigen in CSF by latex
    agglutination
    Negative cryptococcal
    antigen latex test
    Mixed culture of C. neoformans and C. albicans showing the distinctive brown
    colonies of C. neoformans, due to the selective absorption of pigment from the
    media, compared to the white colonies of C. albicans.
    Encapsulated yeast in India ink preparation.
    The small round structure in the center of the white area is the yeast
    cell. 400X.
    India ink preparation of CSF from a patient with cryptococcal meningitis
    showing a budding yeast cell of C. neoformans surrounded by a characteristic
    wide gelatinous capsule.
    Raised skin lesions resulting from dissemination of the
    yeast in an immunocompromised patient.
    C. neoformans yeasts in lung tissue.
    Gram stain, 100X
    Cryptococcosis

    Treatment

    • Systemic fungal agents that cross blood


    brain barrier (BBB)

    • Fluconazole as prophylaxis in AIDS


    patients

    • Combined Amphotericin B & flucytosine


    COCCIDIOIDOMYCOSIS

    Causative agent
    Coccidioides immitis

    Microscopy

    37°C: Spherules filled with endospores

    25°C: hyphae, barrel-shaped arthroconidia


    COCCIDIOIDOMYCOSIS
    Pathogenesis
    • Inhalation of the infectious particle,
    arthroconidia and spherule formation in
    vivo
    • Engulfment within phagosomes by alveolar
    MQs
    • Activation of macrophages (phagosome-
    lysosome fusion) leads to killing
    • Immune complex formation
    deposition leading to local inflammatory
    response
    COCCIDIOIDOMYCOSIS
    Clinical findings
    PRIMARY INFECTION
     Asymptomatic in most cases
     Fever, chest pain, cough, weight loss
     Nodular lesions in lungs

    SECONDARY (DISSEMINATED) INF. (1%)


     Chronic / fulminant
     Infection of lungs, meninges, bones and skin
    COCCIDIOIDOMYCOSIS
    Diagnosis
    Samples: Sputum, tissue
     Direct examination (KOH; H&E)
    2. Culture
    √ SDA: Mould colonies at 25 °C
    √ Spherule production in vitro by
    √ incubation in an enriched medium at
    √ 37°C, 20% CO2
    Alternating arthroconidia. Note annular frill at both ends of
    the separated arthroconidia. Phase contrast
    microscopy, tease mount from colony, 25C
    Sherules and endospores in lung tissue. 1000X.
    Alternating arthroconidia and hyphae. Lactophenol blue
    mount, tease preparation of mould colony, 25C .
    The rash is a immunologic response to the fungus.
    It is most commonly seen in caucasion women.
    COCCIDIOIDOMYCOSIS
    Treatment

    • Amphotericin B
    • Itraconazole
    • Fluconazole (particularly for
    meningitis)
    Features of systemic fungal pathogens

    Organism Culture at 25 0C Culture at 370C Tissue Primary Disseminate


    disease d disease

    C.neoformans Ecapsulated yeast Ecapsulated yeast Ecapsulated yeast pneunonia C. meningitis

    H. Capsulatum Mold, tuberculate Small yeast Small intracellular Pneumonia, RES


    macroconid yeast hilar enlargement
    adenopthay

    B. dermatitidis mold yeast Small yeast pneunonia Skin and


    bone lesions

    C. immitis Mold, spherules spherules Vally fever Pneumonia,


    arthroconidia meningitis
    Skin & bones

    P. brasiliensis mold yeast yeast pneunonia Skin and


    RES
    Case presentation
    A 52 years-old male arrived at an emergency room in a
    disoriented and poorly responsive state with difficult breathing.
    The patient’s history included poorly controlled diabetes and
    chronic obstructive pulmonary disease secondary to cigarette
    smoking. Current medications included steroids his pulmonary
    disease. Physical examination showed that the patient was
    slightly febrile, lethargic, and in respiratory failure. He showed
    deteriorating mental status, and a diagnosis of meningitis was
    considered . A lumber tap produced a CSF sample that on direct
    smear using calcofluor reagent showed encapsulated budding
    yeast. Despite aggressive therapy with amphotericin B and 5-
    flucytosine, the patient’s condition failed to improve. The
    patient died on the third day of hospitalization.

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