Bien Ag Nina Ian John “G” Rachel Mark Jocelle Edo Gienah Jho Kath Aynz Je Glad Nickie

Ricobear Teacher Dadang Niňa Arlene Vivs Paul fie Rico F. Ren Mai Revs Mavis Jepay Yana Mayi Serge Hung Tope

S3 L24: Systemic Mycoses by Dr. Malijan December 17, 2010

These spores become readily airborne, enter the lungs where they
True Systemic (Endemic) Mycoses germinate & develop into large spherules filled with many
Coccidioidomycosis endospores.
Histoplasmosis Rupture of spherule releases the endospores, each of which can
Blastomycosis form new spherule
Paracoccidioidomycosis o Endospores (sporangiospores) are formed within
spherules by repeated cytoplasmic cleavage
GENERAL FEATURES Engulfment within phagosomes by alveolar macrophage
Causative agents: thermally dimorphic fungi that exist in nature, dry Activation of macrophages → phagosome-lysosome fusion → killing
soil Immune complex formation
o Dimorphic – exhibiting the yeast form in infected o Deposition leading to local inflammatory reaction
tissue and the mycelia form in culture or in their o Immunosuppresion resulting from the binding of
natural environment complexes to cells bearing Fc receptors
Geographic distribution varies  From the lungs, dissemination can occur to any
Inhalation → pulmonary infection → dissemination organ of the body where fungi can invade and
Infection is deep within the body or disseminated to internal organs destroy the tissue (bone, CNS)
Caused by true pathogenic fungi capable of infecting healthy
individuals CLINICAL FINDINGS
Primary infection
COCCIDIOIDOMYCOSIS o Asymptomatic in most
o Fever, chest pain, cough, weight loss
Etiology: Coccidioides immitis
o Nodular lesions in lungs
Location: confined to southwestern US, northern Mexico, Central and
Secondary (disseminated) infection – 1%
South America
o Chronic / fulminant
Mycology:
o Infection of lungs, meninges, bones and skin
 Tissue (37o C): spherules filled with endospores
 Cultured on Sabouraud’s agar at 25oC: grows as a mold in 2-3
DIAGNOSIS
weeks; hyphae, barrel-shaped arthroconidia
Samples: sputum, tissue

1. Direct examination (KOH; H&E)

Direct microscopy of skin scrapings from a cutaneous
lesion mounted in 10% KOH and Parker ink solution
The presence of spherules with endospores is
diagnostic
Young spherules have a clear centre with peripheral
cytoplasm and a prominent thick wall
2. Culture
Left: A patient showing the disseminated stage of disease (coccidioidomycosis). Sabouraud’s Dextrose Agar (SDA): mold colonies at
Top right:Spherules. Bottom right:Chains of arthrospores interspersed with empty
25oC
cellular compartments
Spherule production in vitro by incubation in an
enriched medium at 40oC, 20% CO2
In culture, Coccidioides immitis show a suede-like to
downy, greyish white colony with a tan to brown
Grotesque reverse
coccidioidomycosis on face 3. Serology
Latex agglutination
Complement fixation
4. Skin test (coccidioidin and spheruline antigens)

TREATMENT
Symptomatic treatment only (primary infection)
PATHOGENESIS Severe disease:
o Amphotericin B
In the soil, the fungus generates spores by septation of hyphal
filaments (arthrospores / arthroconidia) o Itraconazole
o Fluconazole (particularly for meningitis)

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 Surgical resection of pulmonary cavities
1. Direct examination: Giemsa / Wright
HISTOPLASMOSIS Yeast cells
Etiology: Histoplasma capsulatum Interpretation: positive direct microscopy
Natural reservoir: soil, bat and avian habitats demonstrating characteristic yeast-like cells from
Location: may be prevalent all over the world, but the incidence any specimen should be considered significant
varies widely (most endemic in Ohio, Mississippi, Kentucky) Tissue morphology of H. Capsulatum showing
Mycology: numerous small narrow base budding yeast cells
In tissue (37oC), the spherical yeast are typically seen within inside macrophages
2. Culture
macrophages, as H. Capsulatum is a facultative intracellular
parasite; the hyphae and conidia convert to small, oval yeast Mold at 25oC
cells Conversion to yeast on an enriched medium at 37oC
Hyphae, microconidia and macroconidia (tuberculate 3. Serology
chlamydospore) at 25oC Complement fixation
In culture, hyphae and conidia are seen 4. Skin test
Histoplasmin antigen: limited diagnostic value
AFRICAN HISTOPLASMOSIS
TREATMENT
 Etiology:Histoplasma capsulatum var. duboisii
Acute pulmonary histoplasmosis is managed with supportive
 Differentiation from classical histoplasmosis
therapy and rest
o Larger, thick-walled yeast cells
Disseminated disease: Amphotericin B, Itraconazole
o Pronounced giant cell formation in infected tissue
o Diminished pulmonary involvement
o Greater frequency of skin and bone lesions BLASTOMYCOSIS
Etiology:Blastomyces dermatitidis
Location: America, Africa, Asia
Histiocyte containing Mycology:
numerous yeast cells of Yeasts at 37oC - bud is attached to the parent cell by a broad
Histoplasma capsulatum. base

PATHOGENESIS

Inhalation of infectious particle

Primary cutaneous inoculation
Infiltration of macrophages and neutrophils and granuloma
PATHOGENESIS formation
Inhalation of microconidia / primary cutaneous inoculation Oxidative killing mechanisms of neutrophils and fungicidal
Conversion to budding yeast cells activity of macrophages
Engulfed by alveolar macrophages where they are able to
replicate CLINICAL FINDINGS
Restriction of growth or dissemination to reticuloendothelial Pulmonary infection
system (RES) such as liver, spleen, bone marrow, LN by Chronic cutaneous infection
bloodstream Subcutaneous nodule, ulceration
Suppression of cell-mediated immunity Disseminated infections
CLINICAL FINDINGS Skin, bone, GUT, CNS, spleen
Pulmonary infection Primary cutaneous infection
mild / moderate / severe / chronic cavitary
Disseminated infection DIAGNOSIS
RES (liver, spleen, lymph nodes, bone marrow) Sample: sputum, tissue
Primary cutaneous infection
1. Direct microscopic exam
DIAGNOSIS KOH, H&E: yeast cells
Samples: sputum, tissue, bone marrow, CSF, blood

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 Tissue sections would show large, broad-base, pulmonary disease or dissemination to other organs (mouth
unipolar, budding yeast-like cells, 8-15um in and nose)
diameter. Many patients present with painful oral sores
Tissue sections need to be stained by Grocott’s
methenamine silver method to clearly see the yeast- DIAGNOSIS
like cells, which are often difficult to observe in H&E Sample: sputum, tissue
preparations.
1. Direct microscopic exam
2. Culture KOH, H&E
Mold at 25oC (Sabouraud’s agar: white or brown A positive direct microscopy demonstrating the
colony with branching hyphae bearing conidia) presence of large, 20-60um, round, narrow base
Conversion to yeast (on tissue) or on an enriched budding yeast cells with multiple budding “steering
medium at 37oC wheels” from any specimen should be considered
significant
3. Serology 2. Culture
Immunodiffusion test Mold at 25oC
ELISA to detect antibodies to exoantigen A Conversion to yeast on an enriched medium at 37oC
3. Serology
4. Skin test Immunodiffusion
Blastomycin antigen: limited / no diagnostic value Complement fixation

TREATMENT TREATMENT
Amphotericin B Amphotericin B
Itraconazole Itraconazole
Fluconazole Ketoconazole
Corrective surgery Sulfonamides

PARACOCCIDIOIDOMYCOSIS
Etiology:Paracoccidioides brasiliensis
Location: Central and South America
Mycology:
At 37oC (in tissue): multiple budding yeasts; the buds are
attached to the parent cell by a narrow base
Ship-steering wheel appearance due to presence of multiple
buds
At 25oC: hyphae and conidia

Niña
Ayna

PATHOGENESIS
Inhalation of conidia Turay
More common in males
Ang trans na ito ay
Determinants of pathogenicity Nickie inihahandog ng...
Paul
The fungus has a protein in its cytoplasm which binds only to
estrogen but not to testosterone; this binding prevents
MiCrObIoMaN
conversion to yeast form at 37oC
Yeast cell wall polysaccharides (alpha-glucan) stimulate Edo
granuloma formation Teacher

CLINICAL FINDINGS
Initial nodular lesions occur in the lung
After a period of dormancy (duration variable), pulmonary
granulomas may become active leading to chronic, progressive

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