ENDEMIC MYCOSES/SYSTEMIC MYCOSES

Outlines
General characteristics of True or systemic ( endemic mycosis Coccidioidomycosis Histoplasmosis Blastomycosis Paracoccidioidomycosis Penicillosis
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SYSTEMIC MYCOSES GENERAL CHARACTERISTICS

Inherently virulent and can cause disease in healthy humans Geographic distribution varies Inhalation pulmonary 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

COCCIDIOIDOMYCOSIS
Etio: Coccidioides immitis/posadasii Location: 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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COCCIDIOIDOMYCOSIS Pathogenesis
Grows in the soil, but inhalation of a single spore can initiate infection. 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 contd
Clinical manifestation

Primary infection
Asymptomatic 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

COCCIDIOIDOMYCOSIS contd
Secondary (disseminated) inf. (1%) Chronic / fulminant Infection of lungs, meninges, bones, joint subcutaneous 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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Extension of pulmonary coccidioidomycosis showing a large superficial, ulcerated plaque

Chronic cutaneous coccidioidomycosis showing granulomatous lesions of the face, neck and chin
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COCCIDIOIDOMYCOSIS
Diagnosis
Samples Skin scrapings Sputum and bronchial washings, Cerebrospinal fluid, pleural fluid and blood, Bone marrow, urine Tissue biopsies from various visceral organs

Direct examination
Skin scrapings using 10% KOH and Parker ink or calcofluor white mounts Exudates and body fluids should be centrifuged and the sediment examined using either 10% KOH and Parker ink or calcofluor white mounts Tissue sections should be stained using Periodic acid-Schiff (PAS), 11 Grocott's methenamine silver (GMS) or Gram stain, H&E

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 of Coccidioides 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 by bloodstream 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
Diagnosis
Samples: 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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HISTOPLASMOSIS contd

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 of H. capsulatum var. capsulatum (left) showing numerous small narrow base budding yeast cells (1-5m diam) inside macrophages

H. capsulatum var. duboisii (right) showing larger sized budding yeast cells (5-12 m in diam).

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HISTOPLASMOSIS contd
Treatment Not 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 not detected until the infection has spread to other organs Indolent in onset and patients present with chronic symptoms such as cough, fever, malaise and weight loss Lesions become more extensive, with continued suppuration 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
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.
Ulcerated granuloma due to B. dermatitidis

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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 a broad 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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BLASTOMYCOSIS contd
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 to estrogen but not to testosterone The inf. is more common in males

Yeast cell wall polysaccharides (alpha-glucan) stimulate granuloma 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
DiagnosisSamples: 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. Penicillium 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

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