Systemic Mycoses Graduate School

The Major Mycoses and Causative Fungi

Type of Mycosis Causative Fungal Agents

Mycosis

Endemic (primary, systemic) Paracoccidioides brasiliensis

Paracoccidioidomycosis

Coccidioides immitis, C posadasii 

Coccidioidomycosis

Histoplasma capsulatum  Histoplasmosis

Blastomyces dermatitidis  Blastomycosis

Opportunistic Candida albicans and other Candida species 

Systemic candidiasis

Cryptococcus neoformans  Cryptococcosis

Aspergillus fumigatus and other Aspergillus species 

Aspergillosis

Species of Rhizopus, Absidia, Mucor, and other zygomycetes 

Mucormycosis (zygomycosis)

Penicillium marneffei  Penicilliosis

Systemic vs. Opportunisic

MycosesMYCOSES SYSTEMIC OPPORTUNISTIC

FORMS Dimorphic Monomorphic

GEOGRAPHICAL Environment Normal flora

PORTAL OF ENTRY Lungs Variable

HOST Immunocompetent Immunocompromised

RECOVERY Good  prognosis Poor prognosis

SYSTEMIC MYCOSES

 North American Blastomycosis South American  Blastomycosis Darling’s Disease  San Joaquin Valley Fever

CoccidioidomycosisEtiology Coccidioides immitis, C posadasii 

Ecology Soil

Geographic distribution

Semiarid regions of southwestern United States, Mexico, Central and South America

Conidia (< 35 °C)

Tissue form

Hyaline septate hyphae and arthroconidia, 3 x 6 m

Spherules 37⁰C, 10–80 m or larger, containing endospores, 2–4 m

Branched hyphae w/ alternating arthrospores and empty cells

Cultural Characteristics

• Sabaraud’s Agar incubated at 20-30C

• Colony: white, gray or brownish color with powdery, wooly or cottony texture ( extreme caution should be exercised) 

• Spherules- produced on a complex medioum under 40C 20% CO2  

Coccidioides immitis (SW USA, Latin America)

DiseasesCoccidiomycosis- mild lung infection – asymptomatic or mild pneumonia–  Dissemination leads to bone granulomas or 

meningitis.• Erythema nodosum (red tender nodules on extensor surfaces, indicated DTH rxn to fungal antigens – NO organisms in lesions

• Arthragias- “valley fever”, “desert rheumatism”

Habitat/Trans

• Endemic in arid parts of SW USA, Latin America.

Pathogenesis• Arthrospores are inhaled.• Arthrospores make spherules w/ doubly

refractive wall filled with endospores. • On rupture, endospores released to form new spherules which spread by direct extension or via blood.

Diagnosis

• Skin tests w/ coccidiodin or spherulin

Treatment• Amphotericin B• Itraconazole

HistoplasmosisEtiology Histoplasma capsulatum, Darling’s Disease

Ecology Bat and avian habitats (guano); alkaline soil

Geographic distribution

 Worldwide, but endemic to Ohio, Mississippi river valleys. (Think OHIstOplama) ; central Africa (var duboisii)

Conidia (< 35 °C)Two kinds of asexual spores:

non encapsulated, Hyaline septate hyphae Mold: Tuberculate macroconidia, macroconidia, 8–16 m, and small oval or pyriform (pear shaped) microconidia, 3–5 m

Tissue formsexual stage :Emmonsiella capsulata

Oval yeasts, 2 x 4 m, intracellular in macrophages **** EXOANTIGEN TESTH. capsulatum : H and M bands

• Giemsa and gram staining do not “take” on the cellwalls of H. capsulatum

• cells often appear to be surrounded by an empty areola

• which was incorrectly taken to be a capsule• +   H.capsulatum

Histoplasma capsulatum (Ohio and Mississippi river valleys)

*NOTE:  Sepedonium- a fungi characterized by tuberculate macroconidia 

Difference: no microconidia and it is a monomorphic fungi

   **NOTE:   Leishmania speciesDifference: Leishmania do not stain w/ fungal

 stain and it has a central nuclear body

Pathogenesis

• Inhaled microconidia develop into yeasts within macrophages.

• (Histoplasma Hides in macrophages) Spreads quickly, calcified granulomas.

Diagnosis• Suitable material for diagnostic analysis:

Bronchial secretionUrinescrapings from infection foci

• For microscopic examination:

Giemsa  or Wright staining is applied and yeast cells are looked for inside the macrophages and polymorphonuclear leukocytes.

 Cultures on blood Sabouraud agar must be incubated for several weeks. Antibodies are detected using the complement fixation test and agar gel precipitation. 

The diagnostic value of positive or negative findings in a histoplasmin scratch test is doubtful.

Diagnosis

• ID budding yeasts WITHIN macrophages.

• DTH skin test w/ histoplasmin

Treatment• Amphotericin B• Itraconazole

BlastomycosisEtiology Blastomyces dermatidis 

Ecology Unknown (riverbanks?)

Geographic distribution Endemic along Mississippi, Ohio, and St. Lawrence River Valleys and in Southeastern United States

Conidia (< 35 °C) YEAST FORM : Round yeast w/ doubly refractive wall, single broad based bud

MOLD FORM : Branched hyphae w/ small conidia bearing single globose to piriform conidia, 2–10 m

Tissue form Thick-walled yeasts with broad-based, usually single buds, 8–15 m

North American Blastomycosis/ Gilchrist’s  disease

• RT: Mold: lollipop conidia•  37C: Yeast: yeast cell w/ broad based single budding· ****EXOANTIGEN TEST

Test for:• systemic fungi (immunodiffusion)• B. dermatitidis : appearance of spc. A band

Treatment

• Amphotericin B• Itraconazole

Blastomyces dermatitidis 

A: In tissue or culture at 37 °C.

B: In culture at 30 °C on Sabouraud's agar

Budding yeast cells of Blastomyces dermatitidis in culture. When cultures are incubated at 37°C, large, broad-based budding yeast with a double-contoured all are detected which are characteristic for the yeast phase of this dimorphic fungus. (Lactophenol cotton blue stain; ×400)

Mould form of Blastomyces dermatitidis in culture. The lollipop appearance of the conidium on a conidiophore is characteristic of the environmental mould form for this dimorphic fungus. (Lactophenol cotton blue stain; ×400)

Paracoccidioidomycosis

Etiology Paracoccidioides brasiliensis 

Ecology Soil fungus

Geographic distribution Central and South AmericaLatin America

Conidia (< 35 °C)

YEAST FORM

Tissue form

Hyaline, branched septate hyphae and rare globose conidia and chlamydospores

Round yeast w/ thick wall andmultiple buds

Hyaline, septate hyphae and rare globose conidia and chlamydospores

South American Blastomycosis

Paracoccidioides brasillensis• Dimorphic fungi• RT: Mold: Chlamydoconidia• 37C: Yeast: yeast cell w/ multiple budsPILOT WHEEL/ MARINER’s SHIP WHEEL•  ****EXOANTIGEN TEST:• P. brasilliensis : bands 1, 2, 3

Treatment• Amphotericin B• Itraconazole

OPPORTUNISTIC MYCOSESInfections due to fungi of low virulence in patients who are 

immunologically compromised 

All Monomorphic

Candida

YEAST FORM : Oval yeast w/ single bud and “psuedohyphae”

C. albicans germ tubes w/ chamydospores at 37’C

MOLD FORM : NONE

Characteristics:

Oval yeast w/ singlebud. Can appear as “pseudohyphae” w/in tissue

Habitat/Trans: Normal flora ofupper respiratory, GI, female GU, so NO person-person transmission.

NEVER in the blood

Infections with Candida usually occur when there is some alteration in:

• Cellular immunity• Normal Flora• Physiology

Oral Thrush 

Diseases

Vulvovaginitis- vaginal itching/discharge, favored by high pH, diabetes, antibiotics, oral contraceptives, menses, pregnancy

Cutaneous candidiasis- skin invasion favored bywarmth, moisture: inframammary folds, groin• Oral thrush- white exudate in immunocompromised• Esophogeal candidiasis- AIDS defining illness w/substernal chest pain, dysphagia• Disseminated candidiasis- Immunocompromisedand IVDA

Diagnosis

C.albicansdifferentiated from other Candida by germtubes in serum at 37’C and chlamydospores.

Skin tests are positive in normal adults, indicator of good cellular immunity.

Treatment

• Skin infections w/ topical clotrimazole• vaginitis w/ imidazole suppositories• oral thrush w/ “swish ‘n swallow” nystatin• systemic candidiasis w/ amphotericin B

Cryptococcus

YEAST FORM: Oval budding yeast w/polysccharide capsule

MOLD FORM: NONE

Habitat/Trans

Soil w/ pigeon crap

(Think: cryptoCOCCUS= pigeon CACA)

Pathogenesis:

• Humans inhale Yeast

Cryptococcus neoformans

Diseases

• Usually asymptomatic, can cause pneumonia,bone/skin granulomas. 

Dissemination causes• cryptococcal meningitis, subacute.

Characteristics

Oval budding yeast w/ wide polysaccardidecapsule (India ink stain)

• Virulence factors1. Anti-phagocytic polysaccharide capsule2. Antioxidant melanin3. Ability to grow at 37°C

Cryptococcus neoformans in India ink preparation of spinal fluid. The large capsule is visible

Colonies of Cryptococcus neoformans usually appear mucoid when first isolated. Some strains are poorly

encapsulated and lack the mucoid appearance. (Sabouraud dextrose agar)

Clinical Findings

Chronic meningitisCerebrospinal fluid pressure- elevatedprotein -elevated cell count -elevated glucose -normal or low

Patients may complain   headacheneck stiffnessDisorientation lesions in skin, lungs, or other organs

• The course of cryptococcal meningitis may fluctuate over long periods, but all untreated cases are ultimately fatal.

Diagnostic Laboratory Tests

Specimensspinal fluidtissueExudatesSputum bloodurine

 Spinal fluid is centrifuged before microscopic examination and culture.

• Microscopic Examination– wet mounts, both directly and after mixing with India ink, which delineates the 

capsule.

Diagnostic Laboratory Tests

Culture Cycloheximide inhibits C. neoformanns growth at 37 °C  + urease.  colonies : brown pigment

Serology Tests for capsular antigen can be performed on cerebrospinal fluid and 

serum latex slide agglutination test -  + cryptococcal antigen  Indirect fluorescent antibody

Treatment Combination therapy of amphotericin B   Fluconazole offers excellent penetration of the central nervous system  Highly Active Antiretroviral Therapy (HAART) better prognosis for 

HIV/AIDS

Aspergillus

YEAST FORM: NONE

MOLD FORM: V-shaped septate hyphae w/ radiating chains of conidia

Aspergillus fumigatus

Invasive necrotizing pneumonia in AIDS, Molds grow in pulmonary cavities and produce

Aspergilloma (FUNGUS BALL), requiring surgery.Allergic bronchopulmonaryaspergillosis, type I hypersensitivity reaction like asthma.

A.flavus- grows on cereal or nuts produces aflatoxins (toxic, carcinogenic to liver)

Characteristics

• Septate hyphae, V-shaped branches• Conidia form radiating chains. (compare w/ 

mucor/rhizopus)

Habitat/Trans

• Saprophytic molds

• EVERYWHERE!

Pathogenesis:• Transmission by airborne conidia colonize and invade abraded skin, wounds, burns, ear, cornea

Diagnostic Laboratory Tests

Specimens Sputumother respiratory tract specimens lung biopsy tissue

Microscopic ExaminationKOH or calcofluor white  histologic sections 

• +hyaline, septate, and uniform in width (about 4 m) and branch dichotomously

Culture room temperature - + CONIDIA

Diagnostic Laboratory TestsSerology•  precipitins positive aspergilloma or allergic forms of aspergillosis• circulating cell wall galactomannan is diagnostic.

TreatmentAspergilloma -itraconazole - amphotericin B and surgeryLess severe chronic necrotizing pulmonary disease -voriconazole - itraconazoleAllergic forms of aspergillosis -corticosteroids -disodium chromoglycate

Mucor/Rhizopus

YEAST FORM: NONE

MOLD FORM: Right-angle branched nonseptate

hyphae w/ sporangiumGray to brown to black colony filling a Petri dish in 2 to 3 days. 

Characteristics

• Nonseptate hyphae w/ broad irregular walls and right angle branches (compare w/ aspergillus)

• Endospores inside of sporangium

Diseases

• Rhinocerebral mucormycosis- associated w/ diabetes, caused by infection of nasal mucosa with invasion of sinuses/orbit. Molds proliferate in walls of blood vessels.

• (Think MUCOR/Rhizopus invades MUCOSA)•  Important in immunocompromized patients paricularly leukemic patients

Habitat/Trans

• Saprophytic molds• EVERYWHERE!

Diagnosis:Biopsy

Treatment:Amphotericin B,Surgical resection

Penicillium marneffei

•  A dimorphic fungus grow as mold at 25 °C and as arthroconidia at 37 °C 

• causes tuberculosis-like disease in AIDS patients

• Drug of choice is amphotericin B

• Produces a red pigment