systemic mycoses graduate school
TRANSCRIPT
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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
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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
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SYSTEMIC MYCOSES
North American Blastomycosis South American Blastomycosis Darling’s Disease San Joaquin Valley Fever
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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
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Branched hyphae w/ alternating arthrospores and empty cells
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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
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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”
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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.
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Diagnosis
• Skin tests w/ coccidiodin or spherulin
Treatment• Amphotericin B• Itraconazole
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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
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• 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
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Histoplasma capsulatum (Ohio and Mississippi river valleys)
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*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
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Pathogenesis
• Inhaled microconidia develop into yeasts within macrophages.
• (Histoplasma Hides in macrophages) Spreads quickly, calcified granulomas.
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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.
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Diagnosis
• ID budding yeasts WITHIN macrophages.
• DTH skin test w/ histoplasmin
Treatment• Amphotericin B• Itraconazole
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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
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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
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Blastomyces dermatitidis
A: In tissue or culture at 37 °C.
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B: In culture at 30 °C on Sabouraud's agar
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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)
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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
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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
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OPPORTUNISTIC MYCOSESInfections due to fungi of low virulence in patients who are
immunologically compromised
All Monomorphic
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Candida
YEAST FORM : Oval yeast w/ single bud and “psuedohyphae”
C. albicans germ tubes w/ chamydospores at 37’C
MOLD FORM : NONE
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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
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Infections with Candida usually occur when there is some alteration in:
• Cellular immunity• Normal Flora• Physiology
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Oral Thrush
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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
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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.
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Treatment
• Skin infections w/ topical clotrimazole• vaginitis w/ imidazole suppositories• oral thrush w/ “swish ‘n swallow” nystatin• systemic candidiasis w/ amphotericin B
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Cryptococcus
YEAST FORM: Oval budding yeast w/polysccharide capsule
MOLD FORM: NONE
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Habitat/Trans
Soil w/ pigeon crap
(Think: cryptoCOCCUS= pigeon CACA)
Pathogenesis:
• Humans inhale Yeast
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Cryptococcus neoformans
Diseases
• Usually asymptomatic, can cause pneumonia,bone/skin granulomas.
Dissemination causes• cryptococcal meningitis, subacute.
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Characteristics
Oval budding yeast w/ wide polysaccardidecapsule (India ink stain)
• Virulence factors1. Anti-phagocytic polysaccharide capsule2. Antioxidant melanin3. Ability to grow at 37°C
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Cryptococcus neoformans in India ink preparation of spinal fluid. The large capsule is visible
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Colonies of Cryptococcus neoformans usually appear mucoid when first isolated. Some strains are poorly
encapsulated and lack the mucoid appearance. (Sabouraud dextrose agar)
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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.
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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.
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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
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Aspergillus
YEAST FORM: NONE
MOLD FORM: V-shaped septate hyphae w/ radiating chains of conidia
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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)
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Characteristics
• Septate hyphae, V-shaped branches• Conidia form radiating chains. (compare w/
mucor/rhizopus)
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Habitat/Trans
• Saprophytic molds
• EVERYWHERE!
Pathogenesis:• Transmission by airborne conidia colonize and invade abraded skin, wounds, burns, ear, cornea
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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
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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
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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.
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Characteristics
• Nonseptate hyphae w/ broad irregular walls and right angle branches (compare w/ aspergillus)
• Endospores inside of sporangium
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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
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Habitat/Trans
• Saprophytic molds• EVERYWHERE!
Diagnosis:Biopsy
Treatment:Amphotericin B,Surgical resection
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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
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