Endemic mycoses sevtap Arikan, md



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ENDEMIC MYCOSES

  • Sevtap Arikan, MD


TRUE SYSTEMIC (ENDEMIC) MYCOSES

  • Coccidioidomycosis

  • Histoplasmosis

  • Blastomycosis

  • Paracoccidioidomycosis



TRUE SYSTEMIC MYCOSES General features

  • Causative agents: thermally dimorphic fungi that exist in nature, soil

  • Geographic distribution varies

  • Inhalation pulmonary inf.  dissemination

  • No evidence of transmission among humans or animals

  • Otherwise healthy individuals are infected



COCCIDIOIDOMYCOSIS

  • Etio: Coccidioides immitis

  • Location: Confined to southwestern US, northern Mexico, Central and South America

  • Micr.: Tissue (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 ---killing

  • Immune complex formation

    • deposition leading to local inflammatory rx.s
    • immunosupression resulting from the binding of complexes to cells bearing Fc receptors


COCCIDIOIDOMYCOSIS Clinical findings

  • PRIMARY INF.

  • Asymptomatic in most

  • 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-I

  • Samples: Sputum, tissue

  • 1. Direct examination (KOH; H&E) Spherule

  • 2. Culture

  • SDA: Mould colonies at 25 °C Spherule production in vitro by incubation in an enriched medium at 40°C, 20% CO2



COCCIDIOIDOMYCOSIS Diagnosis-II

  • 3. Serology

  • Tube precipitin (IgM) test

  • Complement fixation

  • Skin test (coccidioidin and spheruline antigens) Negative result may rule out the diagnosis



COCCIDIOIDOMYCOSIS Treatment

  • Symptomatic treatment only (primary infection)

  • Amphotericin B

  • Itraconazole

  • Fluconazole(particularly for meningitis)



HISTOPLASMOSIS

  • 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)

  • Micr. Yeast cell in tissue (37°C)

  • Hyphae, microconidia and macroconidia (tuberculate chlamydospore) at 25 °C



HISTOPLASMOSIS Pathogenesis

  • Inhalation of microconidia / primary cutaneous inoculation

  • Conversion to budding yeast cells

  • Phagocytosis by alveolar macrophages

  • Restriction of growth or dissemination to RES by bloodstream

  • Supression of cell-mediated immunity



HISTOPLASMOSIS Clinical findings

  • PULMONARY INF.

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

  • DISSEMINATED INF.

  • RES (liver, spleen, lymph nodes, bone marrow), mucocutaneous inf.

  • PRIMARY CUTANEOUS INF.



HISTOPLASMOSIS Diagnosis-I

  • Samples: Sputum, tissue, bone marrow, CSF, blood

  • 1. Direct examination: Giemsa / Wright

  • Intra- and extracellular yeast cells

  • 2. Culture: Mould at 25°C

  • Conversion to yeast on an enriched medium at 37°C



HISTOPLASMOSIS Diagnosis-II

  • 3. Serology: Complement fixation...

  • Skin test (Histoplasmin antigen): Limited diagnostic value



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



HISTOPLASMOSIS Treatment

  • Not required for several cases

  • Amphotericin B

  • Itraconazole

  • Surgical resection of pulmonary lesions



BLASTOMYCOSIS

  • Etio: Blastomyces dermatitidis

  • Location: America, Africa, Asia

  • Micr.: Yeasts at 37°C--bud is attached to the parent cell by a broad base

  • Hyphae and conidia at 25 °C



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



BLASTOMYCOSIS Clinical findings

  • ASYMPTOMATIC INF.

  • PULMONARY INF.

  • CHRONIC CUTANEOUS INF. Subcutaneous nodule, ulceration

  • DISSEMINATED INF.

  • Skin, bone, GUT, CNS, spleen

  • PRIMARY CUTANEOUS INF.



BLASTOMYCOSIS Diagnosis-I

  • Samples: Sputum, tissue

  • 1. Direct micr.ic exam: KOH, H&E

  • Yeast cells; bud is attached to the parent cell by a broad base

  • 2. Culture: Mould at 25°C

  • Conversion to yeast on an enriched medium at 37°C



BLASTOMYCOSIS Diagnosis-II

  • 3. Serology: Immunodiffusion test

  • ELISA to detect antibodies to exoantigen A

  • Skin test (Blastomycin antigen) Limited/no diagnostic value



BLASTOMYCOSIS Treatment

  • Amphotericin B

  • Itraconazole

  • Fluconazole

  • Corrective surgery



PARACOCCIDIOIDOMYCOSIS

  • Etio: Paracoccidioides brasiliensis

  • Location: Central and South America

  • Pathogenesis: Inhalation of conidia

  • *The inf. is more common in males

  • Micr.: At 37°C (in tissue ): multiply budding yeasts; the buds are attached to the parent cell by a narrow base

  • At 25 °C: hyphae and conidia



PARACOCCIDIOIDOMYCOSIS Determinants of pathogenicity

  • The fungus has a protein in its cytoplasm which binds only to estrogen but not to testosterone; this binding prevents conversion to yeast form at 37°C.

  • Yeast cell wall polysaccharides (alpha-glucan) stimulate granuloma formation.



PARACOCCIDIOIDOMYCOSIS Clinical findings

  • ASYMPTOMATIC INF.

  • LATENT FORM (duration variable)

  • SYMPTOMATIC INF.

  • Noduler lesions in lungs

  • Dissemination to other organs (rare)



PARACOCCIDIOIDOMYCOSIS Diagnosis-I

  • Samples: Sputum, tissue

  • 1. Direct micr.ic exam.: KOH, H&E

  • multiply budding yeasts; the buds are attached to the parent cell by a narrow base

  • 2. Culture: Mould at 25°C

  • Conversion to yeast on an enriched medium at 37°C



PARACOCCIDIOIDOMYCOSIS Diagnosis-II

  • 3. Serology: Immunodiffusion

  • Complement fixation



PARACOCCIDIOIDOMYCOSIS Treatment

  • Amphotericin B

  • Ketoconazole

  • Itraconazole

  • Sulfonamides



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