Systemic mycoses


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Systemic mycoses

  1. 1. 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
  2. 2. 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
  3. 3. SYSTEMIC MYCOSES North American Blastomycosis South American Blastomycosis Darling’s Disease San Joaquin Valley Fever
  4. 4. 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
  5. 5. Branched hyphae w/ alternating arthrospores and empty cells
  6. 6. 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
  7. 7. 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”
  8. 8. 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.
  9. 9. Diagnosis• Skin tests w/ coccidiodin or spherulinTreatment• Amphotericin B• Itraconazole
  10. 10. 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
  11. 11. • 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
  12. 12. Histoplasma capsulatum(Ohio and Mississippi river valleys)
  13. 13. *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
  14. 14. Pathogenesis• Inhaled microconidia develop into yeasts within macrophages.• (Histoplasma Hides in macrophages) Spreads quickly, calcified granulomas.
  15. 15. 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.
  16. 16. Diagnosis• ID budding yeasts WITHIN macrophages.• DTH skin test w/ histoplasminTreatment• Amphotericin B• Itraconazole
  17. 17. 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
  18. 18. 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
  19. 19. Blastomyces dermatitidisA: In tissue or culture at 37 °C.
  20. 20. B: In culture at 30 °C on Sabourauds agar
  21. 21. 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)
  22. 22. 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
  23. 23. South American BlastomycosisParacoccidioides 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, 3Treatment• Amphotericin B• Itraconazole
  24. 24. OPPORTUNISTIC MYCOSESInfections due to fungi of low virulence in patients who are immunologically compromised All Monomorphic
  25. 25. Candida YEAST FORM : Oval yeast w/ single bud and “psuedohyphae”C. albicans germ tubes w/ chamydospores at 37’CMOLD FORM : NONE
  26. 26. 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
  27. 27. Infections with Candida usually occur when there is some alteration in:• Cellular immunity• Normal Flora• Physiology
  28. 28. Oral Thrush
  29. 29. DiseasesVulvovaginitis- vaginal itching/discharge, favored by high pH, diabetes, antibiotics, oral contraceptives, menses, pregnancyCutaneous 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
  30. 30. DiagnosisC.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.
  31. 31. Treatment• Skin infections w/ topical clotrimazole• vaginitis w/ imidazole suppositories• oral thrush w/ “swish ‘n swallow” nystatin• systemic candidiasis w/ amphotericin B
  32. 32. CryptococcusYEAST FORM: Oval budding yeast w/polysccharide capsuleMOLD FORM: NONE
  33. 33. Habitat/TransSoil w/ pigeon crap(Think: cryptoCOCCUS= pigeon CACA)Pathogenesis:• Humans inhale Yeast
  34. 34. Cryptococcus neoformansDiseases• Usually asymptomatic, can cause pneumonia,bone/skin granulomas.Dissemination causes• cryptococcal meningitis, subacute.
  35. 35. CharacteristicsOval budding yeast w/ wide polysaccardidecapsule (India ink stain)• Virulence factors1. Anti-phagocytic polysaccharide capsule2. Antioxidant melanin3. Ability to grow at 37°C
  36. 36. Cryptococcus neoformans in India inkpreparation of spinal fluid. The large capsule isvisible
  37. 37. Colonies of Cryptococcus neoformans usually appearmucoid when first isolated. Some strains are poorly encapsulated and lack the mucoid appearance. (Sabouraud dextrose agar)
  38. 38. 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.
  39. 39. 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.
  40. 40. 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
  41. 41. AspergillusYEAST FORM: NONEMOLD FORM: V-shaped septate hyphae w/ radiating chains of conidia
  42. 42. Aspergillus fumigatusInvasive 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)
  43. 43. Characteristics• Septate hyphae, V-shaped branches• Conidia form radiating chains. (compare w/ mucor/rhizopus)
  44. 44. Habitat/Trans• Saprophytic molds• EVERYWHERE!Pathogenesis:• Transmission by airborne conidia colonize and invade abraded skin, wounds, burns, ear, cornea
  45. 45. 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
  46. 46. 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
  47. 47. 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
  48. 48. Characteristics• Nonseptate hyphae w/ broad irregular walls and right angle branches (compare w/ aspergillus)• Endospores inside of sporangium
  49. 49. 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
  50. 50. Habitat/Trans• Saprophytic molds• EVERYWHERE!Diagnosis: BiopsyTreatment: Amphotericin B, Surgical resection
  51. 51. 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