Endemic mycoses sevtap Arikan, md

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