SYSTEMIC MYCOSES - Psau ... 11/10/2015 1 SYSTEMIC MYCOSES 1 Systemic mycoses Systemic fungal infections

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  • 11/10/2015




    Systemic mycoses

    Systemic fungal infections are uncommon

    Natural immunity is high; physiologic barriers include:

    1. Skin and mucus membranes

    2. Tissue temperature - fungi grow better at less than

    37°C (mesophiles)

    3. Redox potential - in vivo conditions too reducing for most fungi


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    Infection requires a large inoculum and is affected by the resistance of the host

    • infection often occurs in endemic areas

    • most infections are asymptomatic or self-limiting

    • in immune-compromised hosts, infections are more often fatal (distinction between infection and disease)

    Systemic fungal disease is most often associated with four organisms

    1. Coccidioides immitis

    2. Histoplasma capsulatum

    3. Blastomyces dermatitidis 4. Paracoccidioides brasiliensis

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    Coccidioidomycosis (Vally fever)

    • Coccidioides immitis is considered to be the most virulent of fungal pathogens.

    • Restricted to hot, semi-arid areas of SW USA and Mexico.

    • Grows in the soil, but inhalation of a single spore can initiate infection.


    In infected tissues, C. immitis

    appears as a mixture of hyphae and




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    Coccidioidomycosis: Normally a benign, sub- clinical upper respiratory infection


    In a small percentage of cases, organism disseminates

    from the lungs to a variety of organs, particularly the

    CNS, meanings, skin, soft tissues, and bone.


    In infected tissues, organism is seen as a mixture of

    spherules and endospores.

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    COCCIDIOIDOMYCOSIS • This is primarily an infection of the lungs caused by

    Coccidioides immitis and C. posadasii, two closely related

    dimorphic fungi found in the soil of semi-arid regions

    • In culture and in soil Coccidioides grows as a mould,

    producing large numbers of barrel-shaped arthroconidia,

    which are easily dispersed in wind currents.

    • In the lungs the arthroconidia form spherules which contain

    numerous endospores. Endospores are released by rupture

    of the spherule wall and develop to form new spherules in

    adjacent tissue or elsewhere in the body.

    • In culture the mould colonies are initially moist and white but

    change within 5–12 days to become floccose and pale grey

    or brown.


    Epidemiology of COCCIDIOIDOMYCOSIS

    • Infection is acquired by inhalation; the incubation

    period is 1–3 weeks. The major risk factor for infection is

    environmental exposure.

    • Outbreaks have been associated with ground-disturbing

    activities, such as building construction and

    archaeological excavation, as well as with natural

    events that result in the generation of dust clouds, such

    as earthquakes and dust storms.


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    1. Race: Filipinos > African American> Caucasian

    2. Age: Extremes more susceptible

    3. Sex: Males more susceptible

    4. Pregnancy

    5. Immunosuppression

    Risk factors for disseminated



    Microscopical appearance of

    Coccidioides arthroconidia(4 × 6

    μm diameter)

    Microscopical appearance of Coccidioides

    spherules in tissue (up to 120 μm in



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    Clinical features of COCCIDIOIDOMYCOSIS

    • Coccidioides causes a wide spectrum of disease, ranging

    from a transient pulmonary infection that resolves without

    treatment, to chronic pulmonary infection, or to more

    widespread disseminated disease.

    • About 40% of newly infected persons develop an acute

    symptomatic and often severe influenza-like illness.

    • most otherwise healthy persons recover without treatment,

    their symptoms disappearing in a few weeks. In some cases

    primary infection may result in chronic pulmonary disease.

    • Fewer than 1% of infected individuals develop disseminated

    coccidioidomycosis. This is a progressive disease that

    usually develops within 3–12 months of the initial infection,

    although it can occur much later following reactivation of a

    quiescent infection in an immunosuppressed individual.


    • One or more sites may be involved, but the skin, soft

    tissue, bones, joints and the central nervous system are

    most commonly affected.

    • Meningitis is the most serious complication of

    coccidioidomycosis, occurring in 30–50% of patients with

    disseminated disease. Without therapy, it is almost always



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    1. Suppurative or granulatomas inflammation

    2. Microscopical examination of sputum, pus and biopsy material (Spherule or endospores seen on pathology)

    3. Culture of microorganisms

    4. Complement fixation assay (in cerebrospinal fluid)

    5. Serological tests


    Laboratory diagnosis • Microscopical examination of sputum, pus and biopsy material is helpful

    as the relatively large size and numbers of mature spherules present makes their detection and identification comparatively straightforward.

    • Material for culture should be inoculated on to screw-capped slopes of Sabouraud agar and incubated at 25–30°C for 1–2 weeks. The fungus can be identified by its colonial morphology and the presence of numerous thick-walled arthroconidia formed in chains from alternate cells of the septate hyphae.

    • The arthroconidia are highly infectious and are a serious danger to laboratory staff. Consequently, Petri dishes should never be used for isolation of the organism and all procedures should be carried out in a biological safety cabinet under Category 3 containment.

    • Preparations for microscopy should be made only after wetting the colony to reduce spore dispersal.


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    • Serological tests play an important part in diagnosis.

    • The immunodiffusion test is most useful for detection of early primary infection or exacerbation of existing disease; antibodies appear 1–3 weeks after infection but are seldom detectable after 2–6 months, or in patients with disseminated coccidioidomycosis.

    • The latex agglutination test gives similar results to the immunodiffusion test, but is less specific. Complement fixing antibodies appear 1–3 months after infection and persist for long periods in individuals with chronic or disseminated disease.

    • In most cases the titre is proportional to the extent of infection; failure of the titre to fall during treatment of disseminated coccidioidomycosis is an ominous sign.



    • The historical standard of treatment is intravenous

    amphotericin B, but oral fluconazole is now used to treat

    many patients with skin, soft tissue, bone or joint

    infections. Itraconazole is also effective, but less well

    tolerated. Because oral fluconazole is so much more

    benign than intrathecal amphotericin B, it is now the drug

    of choice for coccidioidal meningitis.

    Amphotericin B, Fluconazole


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    Histoplasmosis (also called cave disease)


    Caused by the dimorphic fungus Histoplasma capsulatum

    Tuberculated macroconidia,grown at 25C Intracellular yeast at 37°C

    Histoplasmosis is characterized by intracellular growth of the

    pathogen in macrophages and a granulomatous reaction in

    tissue. These granulomatous foci may reactivate and cause

    dissemination of fungi to other tissues.

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    Microscopical appearance of Histoplasma

    capsulatum microconidia and macroconidia

    Microscopical appearance of Histoplasma

    capsulatum yeast cells in tissue.




    1.Usually, acute benign respiratory disease

    2.Rarely, progressive, chronic or disseminated disease

    3.Endemic area in U.S. -Atlantic Ocean to N. Dakota (500,000 cases/year in U.S.), except New England & Florida. Most cases in Ohio and Mississippi Rivers)

    • Other endemic regions include parts of Africa, Australia, India and Malaysia.

    H. capsulatum grows in soil.

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