systemic mycosis 06-07
TRANSCRIPT
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Systemic Mycoses
Caustive agents Histoplasma capsulatumBlastomyces dermatitidis Cryptococcus neoformansCoccidioides immitisParacoccidioides brasillensis
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HistoplasmosisCausative Agent Histoplasma capsulatum var capsulatumHistoplasma capsulatum var. duboisii o The organism is misnamed because:
It infects macrophages NOT plasma cells & It is non-capsulated
Morphology Dimorphic fungus Smallest yeast cells Reproduce by budding
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Source of Infection• Soil containing bird or bat excreta• No case to case transmissionPathogenesis• Spores are inhaled, engulfed by
macrophages and develop into yeast forms
• Granulomas formed in the lung which may get calcified like TB
• Disseminate and may infect macrophages in RES (liver, spleen, LN & BM)
Histoplasmosis
Histoplasma yeasts within macrophages
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Clinical Features
• In immunocompetent personso Asymptomatic or flue-like symptomso Chronic lesions in lungs give TB-like picture
• In immunosuppressed personso Disseminated infection o Febrile illnesso Enlargement of RE system,
hepatosplenomagalyo Ulcerated lesions on tongue in AIDS patients
Histoplasmosis
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Lab Diagnosis• Direct examination of sputum • Not helpful as few organisms in sputum• Bone marrow aspirate histology : • Oval yeast cells within macrophages by Giemsa
stain• Culture on Sabouraud’s Dextrose Agar incubate
at 25oC & 37oC to show dimorphic forms• Serology
o An Ab titre of 1:32 with yeast phase Ags is considered diagnostic
• Histoplasmin skin test: Epidemiological value only
• Histopathology of BMA: to see parasitic yeast form
Histoplasmosis
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Oral lesions following hematogenous dissemination
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Macroconidia and microconidia. Phase contrast
microscopy, potato glucose agar, slide culture, 25C.
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Rough-walled macroconidia, Sabouraurd glucose
agar, 25C, lactophenol cotton blue preparation.
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Yeast form growing at 37C in the laboratory. Phase contrast microscopy, 37C, 630X
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Treatment• Oral itraconazole
• Disseminated diseaseo Amphotericin Bo Fluconazole in meningitis
• May need surgical resection of pulmonary lesions
Histoplasmosis
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BLASTOMYCOSISPathogenesis
• Blastomyces dermatitidis • Dimorphic fungusPathogenesis• Inhalation of infectious particles• Cutaneous inoculation• Infiltration of macrophages and
neutrophils and granuloma formation
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BLASTOMYCOSIS Clinical findings
• Asymptomatic • Pulmonary infection • Chronic skin infection • Subcutaneous nodule & ulceration• Disseminated infection • Bone, GUT, CNS, spleen
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Broad based budding yeast
cells, KOH, from a lung
Broad based budding and thickened cell walls and globose shape are
characteristic of the yeast form of
Blastomyces dermatitidis.
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Colony of Blastomyces dermatitidis on Mold Inhibitory Agar after14 days, 30C.
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Skin lesion following dissemination from the lungs.
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The cutaneous lesion developed following dissemination of the fungus from the lungs.
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Treatment
• Amphotericin B• Azoles are alternative in immuocompetent
patients
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Cryptococcosis
Causative agent Cryptococcus neoformans (5µ)o A typical yeast with a thick
capsule (25µ)o Urease positiveSource of infection• Pigeon or birds droppings &
contaminated soil
India Ink Preparation
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Pathogenesis• Capsule is the virulence factor (antiphagocytic)
• Human infection by inhalation
• Most infections are asymptomatic
• May develop pneumonia
• Disseminate to CNS causing meningitis
Cryptococcosis
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Clinical Features• Disease usually affects immunocompromised• Lung infection usually asymptomatic• Cryptococcal meningitis
o Among top four life-threatening infections in AIDSMeningitis• Intermittent headache & dizziness & vomiting• Difficulty in thinking• Slight fever • Slowly progressing to weight loss, impairment of
nerves • May be difficult to diagnose in early stages
Cryptococcosis
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Lab Diagnosis• CSF Examinationo Turbid CSFo Decreased glucose & increased
proteino Increased cell count >100 cells
mostly lymphocyteso India Ink preparation
Yeast cell with a thick capsuleo Periodic acid-Schiff (PAS), detect
fungal elementso Culture on SDA (grows in 48-72 hrs)o Capsular Antigen in CSF by latex
agglutination
Cryptococcosis
India Ink Preparation
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Negative cryptococcal
antigen latex test
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Mixed culture of C. neoformans and C. albicans showing the distinctive brown colonies of C. neoformans, due to the selective absorption of pigment from the
media, compared to the white colonies of C. albicans.
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Encapsulated yeast in India ink preparation.The small round structure in the center of the white area is the yeast
cell. 400X.
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India ink preparation of CSF from a patient with cryptococcal meningitis
showing a budding yeast cell of C. neoformans surrounded by a characteristic wide gelatinous capsule.
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Raised skin lesions resulting from dissemination of the
yeast in an immunocompromised patient.
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C. neoformans yeasts in lung tissue. Gram stain, 100X
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Treatment
• Systemic fungal agents that cross blood brain barrier (BBB)
• Fluconazole as prophylaxis in AIDS patients
• Combined Amphotericin B & flucytosine
Cryptococcosis
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COCCIDIOIDOMYCOSIS
Causative agentCoccidioides immitis
Microscopy
37°C: Spherules filled with endospores
25°C: hyphae, barrel-shaped arthroconidia
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COCCIDIOIDOMYCOSISPathogenesis
• Inhalation of the infectious particle, arthroconidia and spherule formation in vivo
• Engulfment within phagosomes by alveolar MQs
• Activation of macrophages (phagosome-lysosome fusion) leads to killing
• Immune complex formationdeposition leading to local
inflammatory response
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COCCIDIOIDOMYCOSIS Clinical findings
PRIMARY INFECTION Asymptomatic in most cases Fever, chest pain, cough, weight loss Nodular lesions in lungs
SECONDARY (DISSEMINATED) INF. (1%) Chronic / fulminant Infection of lungs, meninges, bones and skin
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COCCIDIOIDOMYCOSIS Diagnosis
Samples: Sputum, tissue
1. Direct examination (KOH; H&E)
2. Culture SDA: Mould colonies at 25 °C Spherule production in vitro by incubation in an enriched medium at 37°C, 20% CO2
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Alternating arthroconidia. Note annular frill at both ends of the separated arthroconidia. Phase contrast
microscopy, tease mount from colony, 25C
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Sherules and endospores in lung tissue. 1000X.
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Alternating arthroconidia and hyphae. Lactophenol blue
mount, tease preparation of mould colony, 25C.
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The rash is a immunologic response to the fungus. It is most commonly seen in caucasion women.
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• Amphotericin B• Itraconazole• Fluconazole (particularly for
meningitis)
COCCIDIOIDOMYCOSIS Treatment
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Organism Culture at 25 0C Culture at 370C Tissue Primary disease
Disseminated disease
C.neoformans Ecapsulated yeast Ecapsulated yeast Ecapsulated yeast pneunonia C. meningitis
H. Capsulatum Mold, tuberculate macroconid
Small yeast Small intracellular yeast
Pneumonia, hilar adenopthay
RES enlargement
B. dermatitidis mold yeast Small yeast pneunonia Skin and bone lesions
C. immitis Mold, arthroconidia
spherules spherules Vally fever Pneumonia,
meningitis
Skin & bones
P. brasiliensis mold yeast yeast pneunonia Skin and RES
Features of systemic fungal pathogens
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Case presentation
A 52 years-old male arrived at an emergency room in a disoriented and poorly responsive state with difficult breathing. The patient’s history included poorly controlled diabetes and chronic obstructive pulmonary disease secondary to cigarette smoking. Current medications included steroids his pulmonary disease. Physical examination showed that the patient was slightly febrile, lethargic, and in respiratory failure. He showed deteriorating mental status, and a diagnosis of meningitis was considered . A lumber tap produced a CSF sample that on direct smear using calcofluor reagent showed encapsulated budding yeast. Despite aggressive therapy with amphotericin B and 5-flucytosine, the patient’s condition failed to improve. The patient died on the third day of hospitalization.