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