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Fungi Causing Systemic Mycoses

Fungi Causing Systemic Mycoses. Dimorphic Fungi. True Systemic (Endemic) Mycoses. Histoplasmosis Blastomycosis Coccidioidomycosis Paracoccioidomycosis. General Features. Causative Agents thermally dimorphic fungi that exist in nature, soil Geographic distribution varies

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Fungi Causing Systemic Mycoses

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  1. Fungi Causing Systemic Mycoses Dimorphic Fungi

  2. True Systemic (Endemic) Mycoses • Histoplasmosis • Blastomycosis • Coccidioidomycosis • Paracoccioidomycosis

  3. General Features • Causative Agents thermally dimorphic fungi that exist in nature, soil • Geographic distribution varies • Inhalation  pulmonary infection  dissemination • No evidence of transmission among humans or animals • Otherwise healthy individuals are infected

  4. blastomycosis

  5. Blastomycosis (Gilchrist’s Disease) Chicago Disease Blastomyces dermatitidis A chronic infection characterized by formation of suppurative & granulomatous lesion found mainly in lungs & disseminate throughout body MOT = Inhalation of airborne spore (conidia)

  6. North American BlastomycosisDistribution • Endemic in North, Central and Southeastern USA, • Quebec province of Canada • V. few cases from India • 1st in 1983 (U.P.) • Scattered cases Mumbai and Vellore.

  7. Blastomyces dermatitides Characteristics: • Dimorphic • Mold in soil, yeast in tissue • Yeast form is round-shaped with a thick refractile wall and a single broad-based bud • Natural habitat is soil rich in organic material • In endemic areas, the fungus lives in soil and rotten wood near lakes and rivers.

  8. Pathogenesis • Infection occurs mainly in the respiratory tract • Inhaled conidia differentiate into yeast cell which initially cause abscesses • Followed by formation of granuloma • Dissemination is rare, but when it occurs skin and bone are the most commonly involved.

  9. Types • Pulmonary –self limiting • Cutaneous-most common, over exposed parts like face, neck and hands. • Disseminated-in AIDS,transplant, immunocompromised • Miscellaneous-rare eg laryngeal, CNS, osteomyelitis

  10. This resembles pulmonary TB showing diffuse infiltration in lung fields

  11. North American Blastomycosis • Cutaneous form exhibits sporotricoidspread and if chronic almost always originates in the lungs. • Most common site of dissemination from lung is the skin. (80% of cases) • Mainly on hands and feet, nodular, draining sinuses or papillomatous and crusted. • LESIONS ARE USUALLY MULTIPLE

  12. Laboratory Diagnosis: • Samples:- sputum,BAL, biopsy, pus from abcess • Direct microscopic examination • (KOH mount) and calcoflour white • = demonstrate characteristic thick walled “yeast cell with single broad-based bud”

  13. Blastomyces dermatitides Broad Based Budding yeast

  14. 2.Culture is difficult, Sabouraud’s dextrose agar, Mycosel and a brain-heart infusion agar to which blood has been added. grows as fluffy, brownish to white fungus which produces pyriform spores

  15. Lab diagnosis cont… • 3. Hypersensitivity test – Blastomycin test • 4. Serological test not useful • 5. DNA probe assay is commercially available • 6. Animal pathogenicity-g.pig,rats,hamster

  16. Treatment • Itraconazole (drug of choice)200-400mg/day for 6mths • Amphotericin B - used to treat severe cases • Surgical excision helpful • Prevention: No vaccine or prophylactic drug available

  17. histoplasmosis

  18. Histoplasmosis • Systemic granulomatous disease • Samuel Taylor Darling- 1905 • Darling’s Disease/"Ohio valley disease," • Caused by inhalation of airborne spores (microconidia) which are present from dropping of birds. • The ecological niche of H. capsulatumis in blackbird roosts, chicken houses and bat guano

  19. Epidemiology • Natural reservoir soil, bat and avian habitats • Location May be prevalent all over the world, but the incidence varies widely • Endemic in Ohio, Kentucky, Mississippi. • In India, the Gangetic West Bengal is the site of most frequent infections, with 9.4 percent of the population testing positive. • Has been isolated from the local soil proving endemicity of histoplasmosis in West Bengal.

  20. Morphology Dimorphic fungus that exist as 1) Yeast cell in tissue and 2) Mold in soil enriched with bird droppings Forms 2 types of asexual spore a) Tuberculate macroconidia (thick-walled finger like projection) b) Microconidia - thin, small, smooth-walled

  21. Pathogenesis • Inhalation of microconidia / primary Cutaneous inoculation • Conversion to budding yeast cells • Phagocytosis by alveolar macrophages • Restriction of growth or dissemination to RES by bloodstream • Suppression of cell-mediated immunity

  22. Clinical Findings • ACUTE PULMONARY INFECTION • Asymptomatic (95%) / mild / moderate / severe /chronic cavitary • CHRONIC PULMONARY • PROGRESSIVE DISSEMINATED INFECTION RES (liver, spleen, lymph nodes, bone marrow), mucocutaneous infection • PRIMARY CUTANEOUS INFECTION

  23. Acute Pulmonary histoplasmosis • Majority are asymptomatic. • incubation period-3-14 days • Fever, chills • Headache • Malaise • Myalgia • Abdominal pain • Cough, Hemoptysis. Dyspnea may also be present

  24. Chronic Pulmonary Histoplasmosis • In pts with underlying pulmonary disease. • Cough • Weight loss • Fever • Malaise • Hemoptysis • dyspnea

  25. Progressive Disseminated Histoplasmosis • In pts who are immunocompromised. • Mucosal ulcers in the -mouth, -gums and -on surfaces of the skin.

  26. Laboratory Diagnosis Samples Sputum, tissue, bone marrow, CSF, blood 1. Direct Examination 2. Culture 3. Serology 4. Skin Test (Histoplasmin antigen) Limited diagnostic value. 5. DNA probe and PCR

  27. Direct Examination • Intracellular (within macrophages) and extracellular oval yeast cells • Stained by H&E for tissue biopsy smear • Yeast may br detected in areas of caseation necrosis and calcified lymph nodes by Gomori Methenamine silver stain.

  28. H&E stain (left) shows macrophages filled with organisms giving the cytoplasm a slightly vacuolated appearance. A GMS (Gomori methenamine stain) (right) shows clustered organisms in cytoplasm.

  29. Budding yeast cell inside macrophages

  30. Culture • Culture of sputum and blood on SDA at 25°C shows cottony mycelial growth. • Thin branching septate hyphae with tuberculoid macroconidia and microconidia • Macroconidia-8-20µm in diameter with fingerlike projections. • At 37°C shows yeast cells.

  31. Tuberculate macroconidia

  32. Serology • Complement fixation test • Immunodiffusion test:- detect antibodies to two glycoprotein's, H and M • Anti-H Ab is more specific and positive in 50-80% of pts • Detection of specific H.capsulatum Ag in urine and serum in immunocompromised pts when Ab production may be impaired

  33. C. Skin test • Histoplasmin test • Mycelial extract as antigen • Useful for epidemiologic determination of incidence of infection • Not used to diagnose actual disease

  34. Treatment: • Amphotericin B – for disseminated infection • Itraconazole - for pulmonary infection • Fluconazole for meningitis. Prevention: None (no vaccine available)

  35. AFRICAN HISTOPLASMOSIS • EtiologyHistoplasma capsulatum var. duboisii Differentiation from Classical Histoplasmosis • Larger, thick-walled yeast cells • Pronounced giant cell formation in infected tissue • Diminished pulmonary involvement • Greater frequency of skin and bone lesions Treatment • Not required for several cases • Amphotericin B • Itraconazole • Surgical resection of pulmonary lesions

  36. EPIZOOTIC HISTOPLASMOSIS • EtiologyHistoplasmacapsulatum var. farciminosum Lymphangitis of horses & mules

  37. Coccidioidomycosis

  38. Coccidiodes immitis • Coccidiodomycosis • San Joaquin Valley Fever, • Desert Fever, • Desert Rheumatism • Endemic in southwest USA, NW Mexico and parts of Central and South America • It is a normal inhabitant of sandy and somewhat saline soil • Disease simulates pneumonia wherein large part of the lung becomes consolidated

  39. History • It is the oldest of the major human mycoses • First case reported by a medical student Alejandro Posadas in 1892 • Coccidia-derived from protozoa • Immitis-im+mitis=not mild

  40. Characteristics • Dimorphic fungus that exist as: • Spherules in tissues containing endospores • Mold at 250C in soil which forms hyphae with alternating arthrospores • Natural habitat is soil

  41. Pathogenesis • MOT: Inhalation of airborne arthrospores • Arthrospores inhaled to the lungs  forms spherules filled with endospore  rupture  endospore release  forms new spherules  disseminate throughout the body

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