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ENDEMIC MYCOSES
Sevtap Arikan, MD
TRUE SYSTEMIC (ENDEMIC)
MYCOSES
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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 ---phagosomelysosome 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
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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 (alphaglucan) 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
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Amphotericin B
Ketoconazole
Itraconazole
Sulfonamides