ENDEMIC MYCOSES

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ENDEMIC MYCOSES

• Sevtap Arikan, MD

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TRUE SYSTEMIC (ENDEMIC) MYCOSES

• Coccidioidomycosis
• Histoplasmosis
• Blastomycosis
• Paracoccidioidomycosis

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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

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COCCIDIOIDOMYCOSIS

• Etio Coccidioides immitis
• Location Confined to southwestern US, northern
  Mexico, Central and South America
• Micr. Tissue (37C) Spherules filled with
  endospores
• 25C hyphae, barrel-shaped arthroconidia

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COCCIDIOIDOMYCOSISPathogenesis

• 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

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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

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COCCIDIOIDOMYCOSIS Diagnosis-I

• Samples Sputum, tissue
• 1. Direct examination (KOH HE)
  Spherule
• 2. Culture
• SDA Mould colonies at 25 C Spherule
  production in vitro by incubation in an
  enriched medium at 40C, 20 CO2

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COCCIDIOIDOMYCOSIS Diagnosis-II

• 3. Serology
• Tube precipitin (IgM) test
• Complement fixation
• Skin test (coccidioidin and spheruline antigens)
  Negative result may rule out the diagnosis

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COCCIDIOIDOMYCOSIS Treatment

• Symptomatic treatment only (primary infection)
• Amphotericin B
• Itraconazole
• Fluconazole(particularly for meningitis)

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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 (37C)
• Hyphae, microconidia and macroconidia
  (tuberculate chlamydospore) at 25 C
  

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HISTOPLASMOSISPathogenesis

• 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

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HISTOPLASMOSISClinical findings

• PULMONARY INF.
• Asymptomatic (95) / mild / moderate / severe/
  chronic cavitary
• DISSEMINATED INF.
• RES (liver, spleen, lymph nodes, bone marrow),
  mucocutaneous inf.
• PRIMARY CUTANEOUS INF.

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HISTOPLASMOSIS Diagnosis-I

• Samples Sputum, tissue, bone marrow, CSF,
  blood
• 1. Direct examination Giemsa / Wright
• Intra- and extracellular yeast cells
• 2. Culture Mould at 25C
• Conversion to yeast on an enriched medium
  at 37C

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HISTOPLASMOSIS Diagnosis-II

• 3. Serology Complement fixation...
• Skin test (Histoplasmin antigen)
  Limited diagnostic value

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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

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HISTOPLASMOSISTreatment

• Not required for several cases
• Amphotericin B
• Itraconazole
• Surgical resection of pulmonary lesions

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BLASTOMYCOSIS

• Etio Blastomyces dermatitidis
• Location America, Africa, Asia
• Micr. Yeasts at 37C--bud is attached to
  the parent cell by a broad base
• Hyphae and conidia at 25 C

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BLASTOMYCOSISPathogenesis

• 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

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BLASTOMYCOSIS Clinical findings

• ASYMPTOMATIC INF.
• PULMONARY INF.
• CHRONIC CUTANEOUS INF. Subcutaneous nodule,
  ulceration
• DISSEMINATED INF.
• Skin, bone, GUT, CNS, spleen
• PRIMARY CUTANEOUS INF.

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BLASTOMYCOSIS Diagnosis-I

• Samples Sputum, tissue
• 1. Direct micr.ic exam KOH, HE
• Yeast cells bud is attached to the parent
  cell by a broad base
• 2. Culture Mould at 25C
• Conversion to yeast on an enriched medium
  at 37C

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BLASTOMYCOSIS Diagnosis-II

• 3. Serology Immunodiffusion test
• ELISA to detect antibodies to
  exoantigen A
• Skin test (Blastomycin antigen) Limited/no
  diagnostic value

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BLASTOMYCOSIS Treatment

• Amphotericin B
• Itraconazole
• Fluconazole
• Corrective surgery

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PARACOCCIDIOIDOMYCOSIS

• Etio Paracoccidioides brasiliensis
• Location Central and South America
• Pathogenesis Inhalation of conidia
• The inf. is more common in males
• Micr. At 37C (in tissue ) multiply budding
  yeasts the buds are attached to the parent
  cell by a narrow base
• At 25 C hyphae and conidia

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PARACOCCIDIOIDOMYCOSISDeterminants 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
  37C.
• Yeast cell wall polysaccharides (alpha-glucan)
  stimulate granuloma formation.

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PARACOCCIDIOIDOMYCOSISClinical findings

• ASYMPTOMATIC INF.
• LATENT FORM (duration variable)
• SYMPTOMATIC INF.
• Noduler lesions in lungs
• Dissemination to other organs (rare)

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PARACOCCIDIOIDOMYCOSISDiagnosis-I

• Samples Sputum, tissue
• 1. Direct micr.ic exam. KOH, HE
• multiply budding yeasts the buds are
  attached to the parent cell by a narrow base
• 2. Culture Mould at 25C
• Conversion to yeast on an enriched medium
  at 37C

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PARACOCCIDIOIDOMYCOSISDiagnosis-II

• 3. Serology Immunodiffusion
• Complement fixation

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PARACOCCIDIOIDOMYCOSISTreatment

• Amphotericin B
• Ketoconazole
• Itraconazole
• Sulfonamides