Aspergillus and systemic mycoses

AspergillosisZygomycosis

HyalohyphomycosisEndemic mycoses

R Lin

Good internet resource

www.drfungus.org

Fungal infections

• Most fungal infections are opportunistic – candida is the most common, causing skin and soft tissue infection– Severe infection (mucous membrane,

oesophagus) in AIDS– Systemic infection in neutropenic

• Aspergillus– Opportunistic, and affects the most severely

neutropenic

Aspergillosis

• Found in the air all around us• Harmless to normal people – we inhale

hundreds of condidia every day• Opportunistic disease in the

immunocompromised patient– Severe neutropenia– Debilitating disease– Disruption of normal flora– Antibiotics, steroids– Abnormal lung e.g. bronchiectasis, cancer

Aspergillus

• >200 species

• Associated with disease: *A. fumigatus, A. flavus, A. niger

• Less common: A. nidulans, A. terreus, A. oryzae, A. ustus, A. versicolor

Laboratory identification

• Grows on Sabouraud agar

• Colony – colour: black, yellow, green, white, red, brown

• 3 structures to recognize– Mycelium - branching, hyaline, septate– Condial head – Condidia : shape and arrange help identify

species

A. fumigatusA. flavus

A. niger

Spectrum of disease

• Colonization: sinuses, lungs• Toxicosis: aflatoxin (A. flavus)• Allergic bronchopulmonary aspergillosis:

sinuses, lungs• Pulmonary aspergilloma: pre-existing lung

cavity• Invasive aspergillosis: pulmonary, sinonasal,

central nervous system, endocarditis, renal• Others e.g. otomycosis (A. niger)

Invasive aspergillosis

• Most commonly in severely neutropenic e.g. after bone marrow transplant

• Portal of entry: sinuses, lungs• Difficult to diagnose

– Clinical suspicion, radiology, laboratory tests

• Difficult to treat– Amphotericin B, voriconazole, itraconazole– Surgical resection

• Poor outcome

Laboratory investigation

• Microscopy: KOH prep, sputum, bronchoalveolar lavage

• Histology: lung

• Culture: sputum (contaminant?), BAL, tissue

• Galactomannan EIA

• PCR: 18sRNA gene, not always useful

Galactomannan EIA

• Monitor post-transplant

• patient 2x / week

• Rising value or high value + symptoms

• False-positives– Penicillin-containing antibiotic– Milk, cereals

Zygomycosis

Rhizopus arrhizus (oryzae)

• Title: Characteristic sporangial production• Disease(s): Zygomycosis

• Legend: Nodal rhizoids, sporangiophore, “umbrella-shaped” collapsed columella, and sporangiospores.

Potato flakes agar tease mount. Color enhanced.

• Genus/Species: Rhizopus arrhizus (oryzae)• Image Type: Microscopic Morphology

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Mucor speciesh

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• Slide Reference #: GK 593• Genus/Species: Mucor species

• Disease(s): Systemic Zygomycosis (Mucormycosis)

• Image Type: Microscopic Morphology

Many species

• e.g. Mucor spp., Absidia spp., Rhizopus spp., Rhizomucor spp., Cunninghamella spp.

• Widely found in the environment

• Immunocompromised patients at risk (as for aspergillus), trauma patients

Zygomycosis: disease

• Invade the bloodstream – disseminated disease

• Local invasion – pulmonary, rhinocerebral

• Intravenous drug use - cerebral infection

• Cutaneous – burns, trauma

treatment

• Very high mortality - 96% for disseminated disease

• Surgery and antifungals

Zygomycosis – laboratory diagnosis• Tissue – histology

• Culture from deep sites (beware contamination!) e.g. rhinocerebral, BSL

• That’s all we have lab tests!

“Hyalohyphomycosis”

• Hyaline septate hyphae

• Non-pigmented

• No differentiating features

• Many species of fungi

• When cultured – some are distinct and can be identified

e.g. Fusarium sp.

• Common in soil, plant, environment

• Typical macroconidia

• cause– Keratitis e.g. with contact lens– Invasive disseminated disease in

neutropenic– Skin and subcutaneous lesions in

disseminated disease

Fusarium dimerum

• Title: ---• Disease(s): ---

• Legend: ---

• Genus/Species: Fusarium dimerum• Image Type: Microscopic Morphology

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e.g. Penicillium marneffei

• Most penicillium harmless

• P. marneffei– Dimorphic – yeast 37 deg C, mould 25 deg C– Disseminated to the blood in AIDS patients in

SE Asia– Fever, skin, liver, spleen, multi-organ

Penicillium marneffeih

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• Slide Reference #: GK 488• Genus/Species: Penicillium marneffei • Disease(s): Penicilliosis marneffei• Image Type: Macroscopic Morphology

Penicillium marneffeih

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• Slide Reference #: GK 489• Genus/Species: Penicillium marneffei • Disease(s): Penicilliosis marneffei• Image Type: Microscopic Morphology

Pigmented moulds

• Dihydroxynaphthalene melanin in their cell walls

• Many many species of fungi• Many types of infection – skin, brain, lung

etc• Chronic tissue infections

– chromoblastomycosis– mycetoma

Curvularia lunatah

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• Slide Reference #: GK 472• Genus/Species: Curvularia lunata

• Disease(s): Mycotic keratitis• Image Type: Microscopic Morphology

Madurella grisea

• Title: Mycetoma• Disease(s): Mycetoma

• Legend: Sclerotium in tissue of the foot, H & E stain.

• Genus/Species: Madurella grisea• Image Type: Histopathology

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Madurella mycetomatis

• Title: Mycetoma• Disease(s): Mycetoma

• Legend: Multiple draining sinuses, swollen tissue, and sclerotia are present.

• Genus/Species: Madurella mycetomatis• Image Type: Clinical Presentation

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ENDEMIC MYCOSES

• Coccidioidomycosis• Histoplasmosis• Blastomycosis• Paracoccidioidomycosis

Endemic mycoses

• thermally dimorphic fungi– As moulds in the soil– Yeast forms in the human body (37 deg C)

• Geographic distribution varies• Inhalation pulmonary INFECTION

dissemination • No evidence of transmission among humans

or animals• Otherwise healthy individuals are infected

Endemic mycoses

• Geographical location is important. Get history of travel; except histoplasmosis (worldwide)

• Clinical suspicion: liver/spleen/lungs/ mucocutaneous involved

• May have no symptoms• Route of infection: through lungs or direct

inoculation of skin• Cause skin lesions, pneumonia, liver/spleen

Tests for systemic mycoses

• Microscopy• Fungal culture (2 temperatures!)• Tissue: histopathology• Serology – often older methods like

immunodiffusion, complement fixation• Skin test of limited value• Others: urinary antigen (e.g.

histoplasma)

COCCIDIOIDOMYCOSISAetiology: Coccidioides immitis

Location: Confined to southwestern US, northern Mexico, Central and South America

Microscopy

-Tissue 37°C: Spherules filled with endospores

- 25°C: hyphae, barrel-shaped arthroconidia

Case historyA 71-year-old male subject regularly spends several winter

months in Arizona to play golf in the sun. Last March he experienced a gradual onset of fever and a headache,

followed by a non-productive cough, myalgia and profound fatigue. His local physician diagnosed bronchopneumonia on chest radiograph, and prescribed azithromycin. The antibiotic provided no benefit, and ultimately the patient received two more courses of different empiric antibiotics. He returned home with continued cough and fatigue, even though the

fever had abated somewhat. Two months following the initial onset of symptoms, a bronchoscopy was performed, and

cultures grew Coccidioides species.

Other presentationsMonths to years following a symptomatic or asymptomatic

infection, the affected lung may show complete resolution or an area of calcified or uncalcified pulmonary nodule similar

radiographically to cancer. Microscopic examination of excised tissue identifies the organism. Occasionally the nodule liquefies to form a thin-walled cavity, which may close spontaneously or remain and become a nidus for

suprainfection or spontaneous pneumothorax. Extrapulmonary dissemination can be identified in nearly all tissues, although skin and soft tissue, bones and meninges

are the most common sites of dissemination. Chronic fibrocavitary pneumonia is seen infrequently, with chronic cough and dyspnoea, night sweats and weight loss, and

lung fibrosis with thick-walled cavities.

From BMJ Best Practice

Coccidioides immitis

Coccidioides immitis

Disseminated coccidioidomycosis

Histoplasma capsulatum

HISTOPLASMOSIS• Aetiology: Histoplasma capsulatum

• Natural reservoir: soil, bat and avian habitats• Location: May be prevalent all over the world, but

the incidence varies widely • Microscopy

– Yeast cell in tissue (37°C)– Hyphae, microconidia and macroconidia

(tuberculate chlamydospore) at 25 °C

Histoplasma capsulatum

Histoplasma

Blastomyces dermatitidis

BLASTOMYCOSIS

• Aetiology: Blastomyces dermatitidis

• Location: America, Africa, Asia

• Microscopy: – Yeasts at 37°C: bud is attached to the

parent cell by a broad base – Hyphae and conidia at 25 °C

Blastomycosis

Paracoccidioides brasiliensis

PARACOCCIDIOIDOMYCOSIS

• Aetiology: Paracoccidioides brasiliensis• Location: Central and South America• Pathogenesis: Inhalation of conidia• Microscopy

– 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