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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 or animals pulmonary inf. dissemination • No evidence of transmission among humans • Otherwise healthy individuals are infected
COCCIDIOIDOMYCOSIS
Etio:
Coccidioides immitis
Location: northern Mexico, Central and South America Micr.: Confined to southwestern US, 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.
Chronic / fulminant (1%) 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% CO 2
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: habitats • Location: world, but the incidence varies widely (most endemic in Ohio, Mississipi, Kentucky) • Micr. soil, bat and avian May be prevalent all over the 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:
Intra- and extracellular yeast cells
2. Culture:
Giemsa / Wright 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- attached to the parent cell by a broad base bud is 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