Post on 02-Apr-2018
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ENDEMIC MYCOSES/SYSTEMIC
MYCOSES
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Outlines General characteristics ofTrue or systemic ( endemic
mycosis
Coccidioidomycosis
Histoplasmosis
Blastomycosis
Paracoccidioidomycosis
Penicillosis
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SYSTEMIC MYCOSES GENERAL
CHARACTERISTICS
Inherently virulent and can cause disease in healthyhumans
Geographic distribution varies
Inhalationpulmonary inf. dissemination
No evidence of transmission among humans or animals
Causative agents: thermally dimorphic fungi that exist
in nature, soil
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SYSTEMIC MYCOSES Contd
Most infections are asymptomatic or self-limiting
In immune-compromised hosts, infections are more
often fatal
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COCCIDIOIDOMYCOSIS
Etio:Coccidioides immitis/posadasiiLocation: Confined to south-western
US, Northern Mexico, Central
and South America
Micr: Tissue(37C):Spherules filled with endospores
25C: hyphae, barrel-shaped arthroconidia
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COCCIDIOIDOMYCOSISPathogenesis
Grows in the soil, but inhalation of a single spore caninitiate infection.
Inhalation of the infectious particle, arthroconidia andspherule formation in vivo
Engulfment within phagosomes by alveolar MQs
Activation of macrophages ---phagosome-lysosomefusion ---killing
Immune complex formation
deposition leading to local inflammatory rx.s
immunosupression resulting from the binding ofcomplexes to cells bearing Fc receptors
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COCCIDIOIDOMYCOSIS contd
Clinical manifestation
Primary infectionAsymptomatic in most cases
The most common symptoms include cough, fever, chest pain,headache, fatigue, chills, malaise, and anorexia
Nodular lesions in lungs
Cutaneous infection acquired via a percutaneous route
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COCCIDIOIDOMYCOSIS contd
Secondary (disseminated) inf. (1%)
Chronic / fulminant
Infection of lungs, meninges, bones, jointsubcutaneous and cutaneous tissues
Lesions in the skin and subcutaneous tissues
occur in more than 65% of cases
May present as small papular nodules, ulcerated
nodules, or verrucous granuloma
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Chronic cutaneous coccidioidomycosis
showing granulomatous lesions of the face,
neck and chin
Extension of pulmonary coccidioidomycosisshowing a large superficial, ulcerated plaque
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COCCIDIOIDOMYCOSISDiagnosisSamples
Skin scrapingsSputum and bronchial washings,
Cerebrospinal fluid, pleural fluid and blood,
Bone marrow, urine
Tissue biopsies from various visceral organsDirect examination
Skin scrapings using 10% KOH and Parker ink or calcofluorwhite mounts
Exudates and body fluids should be centrifuged and the sedimentexamined using either 10% KOH and Parker ink or calcofluorwhite mounts
Tissue sections should be stained using Periodic acid-Schiff (PAS),
Grocott's methenamine silver (GMS) or Gram stain, H&E
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COCCIDIOIDOMYCOSIS contd
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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cutaneous lesion mounted
in 10% KOH and Parker ink Culture ofCoccidioides immitis showing a
suede-like todowny, greyish white colony
with a tan to brown reverse
Tissue section showing typical
endosporulating spherules of
Coccidioides immitis
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COCCIDIOIDOMYCOSIS contd
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 contd
Treatment
Symptomatic treatment only (primary infection)
Amphotericin B Itraconazole
Fluconazole (particularly for meningitis)
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HISTOPLASMOSIS
Histoplasmosis is an intracellular mycotic
infection of the reticuloendothelial system
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)
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HISTOPLASMOSIS contd
Micr.
Yeast cell in tissue (37C)
Hyphae, microconidia and macroconidia
(tuberculate chlamydospore) at 25 C
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HISTOPLASMOSIS contd
Pathogenesis
Inhalation of microconidia / primary cutaneous
inoculation
Conversion to budding yeast cells
Phagocytosis by alveolar macrophages
Restriction of growth or dissemination to RES bybloodstream
Supression of cell-mediated immunity
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HISTOPLASMOSIS contd
Clinical Manifestation
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 of the lower gum showing
ulcer around base of the teeth
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HISTOPLASMOSIS contd
DiagnosisSamples:Sputum, tissue, bone marrow, CSF, blood
1. Direct examination:Giemsa / Wright
Intra- and extracellular yeast cells
Inside the macrophages and polymorphonuclear
leukocytes
2. Culture:Mould at 25C
Conversion to yeast on an enriched medium at 37C
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HISTOPLASMOSIScontd
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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Tissue morphology ofH. capsulatum var. capsulatum (left) showing
numerous small narrow base budding yeast cells (1-5m diam)
inside macrophages
H. capsulatum var. duboisii(right) showinglarger sized budding yeast cells (5-12 m in diam).
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HISTOPLASMOSIS contd
TreatmentNot required for several cases
Amphotericin B
Itraconazole
Surgical resection of pulmonary lesions
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BLASTOMYCOSIS
Granulomatous mycotic infection
Predominantly involves lungs and skin
can spread to other organs
Most prevalent in males 40-60 years of age and
children.
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BLASTOMYCOSIS contd
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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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
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BLASTOMYCOSIS
Clinical manifestation 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 Contd
Pulmonary blastomycosis
In most individuals pulmonary lesions asymptomatic notdetecteduntil the infection has spread to other organs
Indolent in onset and patients present with chronicsymptoms suchas cough, fever, malaise and weight loss
Lesions become more extensive, with continuedsuppuration and eventual necrosis and cavitation
Occasional an acute onset of infection, with development of high fever, chills, productive cough,
myalgia, arthralgia and pleuritic chest pain
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BLASTOMYCOSIS Contd
Ulcerated granuloma due to
B. dermatitidis
Cutaneous blastomycosis
Haematogenous spread gives rise to
cutaneous lesions in over 70% of patients
Lesion tend to be painless and present
either as raised verrucous lesions with
irregular borders, or as ulcers
The face, upper limbs, neck and scalp
are the most frequent sites involved.
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BLASTOMYCOSIS Contd
Diagnosis
Samples:Sputum, tissue
1. Direct micr. exam:KOH, H&E
Yeast cells; bud is attached to
the parent cell by abroad base
2. Culture:Mould at 25C
Conversion to yeast on an enriched medium at 37C
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BLASTOMYCOSIS
Diagnosis
3. Serology:Immunodiffusion test
ELISA to detect antibodies to exoantigen A
Skin test (Blastomycin antigen)
Limited/no diagnostic value
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BLASTOMYCOSIScontd
Treatment
Amphotericin B
Itraconazole
Fluconazole
Corrective surgery
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PARACOCCIDIOIDOMYCOSIS
Etio:Paracoccidioides brasiliensis
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
Location:
Central and South America
The disease is more
common in warm and moist
climates
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PARACOCCIDIOIDOMYCOSIS contd
Pathogenesis: Inhalation of conidia
Determinants of pathogenicity
Has a protein in its cytoplasm which binds only toestrogen but not to testosterone
The inf. is more common in males
Yeast cell wall polysaccharides (alpha-glucan) stimulategranuloma formation
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PARACOCCIDIOIDOMYCOSIS contd
Clinical manifestation Asymptomatic inf.
Latent form (duration variable)
Symptomatic inf.
Noduler lesions in lungs
Dissemination to other organs (rare)
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PARACOCCIDIOIDOMYCOSIS contd
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PARACOCCIDIOIDOMYCOSIS contd
Diagnosis-
Samples: Sputum, tissue
1. Direct micr exam.:KOH, H&E 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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PARACOCCIDIOIDOMYCOSIS contd
3. Serology:Immunodiffusion
Complement fixation
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PARACOCCIDIOIDOMYCOSIS Contd
Treatment
Amphotericin B
Ketoconazole
Itraconazole
Sulfonamides
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Penicillosis
Important OIs in AIDS patients in in south east
Asia, Thailand
Etio. Penici l l ium marneffei
Location : South east Asia
Thailand
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Penicillosis Contd
Reservoir: bamboo rat
Endemic season: rainy season
Route of infection: inhalation
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Penicillosis Contd
Clinical manifestation
Symptoms: fever, chill, cough, chest pain, weight
loss
Lesion the lung, skin lesions (face, arm, neck, torso
Disseminated infection (more frequent)
Hepatomegaly, lymphadenopathy, lesion
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Penicillosis Contd
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Penicillosis Contd
Diagnosis
A Giemsa stained touch smear of a skin biopsy or bone
marrow aspirate is a rapid and sensitive diagnostic
Histopathologic exam and culture of skin, lymph node,bone marrow
Demonstrates the presence of typical
yeast-like cells with a central septa
Yeast-cells are spherical to ellipsoidal
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Penicillosis Contd
Treatment
Amphotericin B
Itraconazole
Secondary prophylaxis in AIDS
Itraconazole