The Major Mycoses and Causative FungiType of Mycosis Causative Fungal Mycosis Agents Endemic Paracoccidioidomycosis Paracoccidioides brasiliensis(primary, systemic) Coccidioides immitis, C Coccidioidomycosis posadasii Histoplasma capsulatum Histoplasmosis Blastomyces dermatitidis Blastomycosis Opportunistic Candida albicans and other Systemic candidiasis Candida species Cryptococcus neoformans Cryptococcosis Aspergillus fumigatus and other Aspergillosis Aspergillus species Species of Rhizopus, Absidia, Mucormycosis (zygomycosis) Mucor, and other zygomycetes Penicillium marneffei Penicilliosis
Systemic vs. Opportunisic Mycoses MYCOSES SYSTEMIC OPPORTUNISTIC FORMS Dimorphic Monomorphic GEOGRAPHICAL Environment Normal floraPORTAL 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 posadasiiEcology SoilGeographic Semiarid regions of southwesterndistribution United States, Mexico, Central and South AmericaConidia (< 35 °C) Hyaline septate hyphae and arthroconidia, 3 x 6 mTissue form 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)Diseases Coccidiomycosis- 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.
HistoplasmosisEtiology Histoplasma capsulatum, Darling’s DiseaseEcology Bat and avian habitats (guano); alkaline soilGeographic Worldwide, but endemic to Ohio, Mississippidistribution river valleys. (Think OHIstOplama) ; central Africa (var duboisii)Conidia (< 35 °C) non encapsulated, Hyaline septate hyphaeTwo kinds of asexual Mold: Tuberculate macroconidia,spores: macroconidia, 8–16 m, and small oval or pyriform (pear shaped) microconidia, 3–5 mTissue form Oval yeasts, 2 x 4 m, intracellular in macrophagessexual stage : **** EXOANTIGEN TESTEmmonsiella H. capsulatum : H and M bandscapsulata
• 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 species Difference: Leishmania do not stain w/ fungalstain 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 secretion Urine scrapings 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/ histoplasminTreatment• Amphotericin B• Itraconazole
BlastomycosisEtiology Blastomyces dermatidisEcology Unknown (riverbanks?)Geographic distribution Endemic along Mississippi, Ohio, and St. Lawrence River Valleys and in Southeastern United StatesConidia (< 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 mTissue 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 TESTTest for:• systemic fungi (immunodiffusion)• B. dermatitidis : appearance of spc. A bandTreatment• Amphotericin B• Itraconazole
Blastomyces dermatitidisA: In tissue or culture at 37 °C.
Budding yeast cells of Blastomyces Mould form of Blastomyces dermatitidis indermatitidis in culture. When cultures are culture. The lollipop appearance of theincubated at 37°C, large, broad-based conidium on a conidiophore is characteristicbudding yeast with a double-contoured all of the environmental mould form for thisare detected which are characteristic for dimorphic fungus. (Lactophenol cotton bluethe yeast phase of this dimorphic fungus.(Lactophenol cotton blue stain; ×400) stain; ×400)
ParacoccidioidomycosisEtiology Paracoccidioides brasiliensisEcology Soil fungusGeographic distribution Central and South America Latin AmericaConidia (< 35 °C) Hyaline, branched septate hyphae and rare globose conidia and chlamydospores Round yeast w/ thick wall andYEAST FORM multiple buds Hyaline, septate hyphae and rare globoseTissue form conidia and chlamydospores
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’CMOLD FORM : NONE
Characteristics:Oval yeast w/ singlebud. Can appear as “pseudohyphae” w/in tissueHabitat/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
Cryptococcus neoformans in India inkpreparation of spinal fluid. The large capsule isvisible
Colonies of Cryptococcus neoformans usually appearmucoid when first isolated. Some strains are poorly encapsulated and lack the mucoid appearance. (Sabouraud dextrose agar)
Clinical FindingsChronic meningitis Cerebrospinal fluid pressure- elevated protein -elevated cell count -elevated glucose -normal or lowPatients may complain headache neck stiffness Disorientation 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 TestsSpecimens spinal fluid tissue Exudates Sputum blood urineSpinal 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 TestsCulture Cycloheximide inhibits C. neoformanns growth at 37 °C + urease. colonies : brown pigmentSerology Tests for capsular antigen can be performed on cerebrospinal fluid and serum latex slide agglutination test - + cryptococcal antigen Indirect fluorescent antibodyTreatment 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 fumigatusInvasive necrotizing pneumonia in AIDS, Molds grow in pulmonary cavities and produceAspergilloma (FUNGUS BALL), requiring surgery.Allergic bronchopulmonaryaspergillosis, type I hypersensitivity reaction like asthma.A.flavus- grows on cereal or nuts producesaflatoxins (toxic, carcinogenic to liver)
Habitat/Trans• Saprophytic molds• EVERYWHERE!Pathogenesis:• Transmission by airborne conidia colonize and invade abraded skin, wounds, burns, ear, cornea
Diagnostic Laboratory TestsSpecimens Sputum other respiratory tract specimens lung biopsy tissueMicroscopic Examination KOH or calcofluor white histologic sections • +hyaline, septate, and uniform in width (about 4 m) and branch dichotomouslyCultureroom 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/RhizopusYEAST FORM: NONEMOLD FORM: Right- angle branched nonseptate Gray to brown to black colony filling a Petri dish in 2 to 3 days.hyphae w/ sporangium
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
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