Systemic Mycoses
Caustive agents
Histoplasma capsulatum
Blastomyces dermatitidis
Cryptococcus neoformans
Coccidioides immitis
Paracoccidioides brasillensis
Histoplasmosis
Causative Agent
Histoplasma capsulatum var capsulatum
Histoplasma 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
Histoplasmosis
Source of Infection
• Soil containing bird or bat excreta
• No case to case transmission
Pathogenesis
• Spores are inhaled, engulfed by
macrophages and develop into yeast
forms Histoplasma yeasts
• Granulomas formed in the lung which within macrophages
may get calcified like TB
• Disseminate and may infect
macrophages in RES (liver, spleen,
LN & BM)
Histoplasmosis
Clinical Features
• In immunocompetent persons
o Asymptomatic or flue-like symptoms
o Chronic lesions in lungs give TB-like picture
• In immunosuppressed persons
o Disseminated infection
o Febrile illness
o Enlargement of RE system, hepatosplenomagaly
o Ulcerated lesions on tongue in AIDS patients
Histoplasmosis
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
Oral lesions following hematogenous
dissemination
Macroconidia and microconidia. Phase contrast
.
microscopy, potato glucose agar, slide culture, 25C
Rough-walled macroconidia, Sabouraurd glucose
agar, 25C, lactophenol cotton blue preparation.
Yeast form growing at 37C in the laboratory.
Phase contrast microscopy, 37C, 630X
Histoplasmosis
Treatment
• Oral itraconazole
• Disseminated disease
o Amphotericin B
o Fluconazole in meningitis
• May need surgical resection of pulmonary lesions
BLASTOMYCOSIS
Pathogenesis
• Blastomyces dermatitidis
• Dimorphic fungus
Pathogenesis
• Inhalation of infectious particles
• Cutaneous inoculation
• Infiltration of macrophages and neutrophils
and granuloma formation
BLASTOMYCOSIS
Clinical findings
• Asymptomatic
• Pulmonary infection
• Chronic skin infection
• Subcutaneous nodule & ulceration
• Disseminated infection
• Bone, GUT, CNS, spleen
Broad based budding and thickened
Broad based budding yeast cell walls and globose shape are
characteristic of the yeast form of
cells, KOH, from a lung
Blastomyces dermatitidis.
Colony of Blastomyces dermatitidis on Mold
Inhibitory Agar after14 days, 30C.
Skin lesion following dissemination from the lungs.
The cutaneous lesion developed following
dissemination of the fungus from the lungs.
Treatment
• Amphotericin B
• Azoles are alternative in immuocompetent
patients
Cryptococcosis
Causative agent
India Ink Preparation
Cryptococcus neoformans (5µ)
o A typical yeast with a thick capsule
(25µ)
o Urease positive
Source of infection
• Pigeon or birds droppings &
contaminated soil
Cryptococcosis
Pathogenesis
• Capsule is the virulence factor (antiphagocytic)
• Human infection by inhalation
• Most infections are asymptomatic
• May develop pneumonia
• Disseminate to CNS causing meningitis
Cryptococcosis
Clinical Features
• Disease usually affects immunocompromised
• Lung infection usually asymptomatic
• Cryptococcal meningitis
o Among top four life-threatening infections in AIDS
Meningitis
• 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
Lab Diagnosis
• CSF Examination
India Ink Preparation
o Turbid CSF
o Decreased glucose & increased protein
o Increased cell count >100 cells mostly
lymphocytes
o India Ink preparation
Yeast cell with a thick capsule
o Periodic acid-Schiff (PAS), detect
fungal elements
o Culture on SDA (grows in 48-72 hrs)
o Capsular Antigen in CSF by latex
agglutination
Negative cryptococcal
antigen latex test
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.
Encapsulated yeast in India ink preparation.
The small round structure in the center of the white area is the yeast
cell. 400X.
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.
Raised skin lesions resulting from dissemination of the
yeast in an immunocompromised patient.
C. neoformans yeasts in lung tissue.
Gram stain, 100X
Cryptococcosis
Treatment
• Systemic fungal agents that cross blood
brain barrier (BBB)
• Fluconazole as prophylaxis in AIDS
patients
• Combined Amphotericin B & flucytosine
COCCIDIOIDOMYCOSIS
Causative agent
Coccidioides immitis
Microscopy
37°C: Spherules filled with endospores
25°C: hyphae, barrel-shaped arthroconidia
COCCIDIOIDOMYCOSIS
Pathogenesis
• 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 formation
deposition leading to local inflammatory
response
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
COCCIDIOIDOMYCOSIS
Diagnosis
Samples: Sputum, tissue
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
Alternating arthroconidia. Note annular frill at both ends of
the separated arthroconidia. Phase contrast
microscopy, tease mount from colony, 25C
Sherules and endospores in lung tissue. 1000X.
Alternating arthroconidia and hyphae. Lactophenol blue
mount, tease preparation of mould colony, 25C .
The rash is a immunologic response to the fungus.
It is most commonly seen in caucasion women.
COCCIDIOIDOMYCOSIS
Treatment
• Amphotericin B
• Itraconazole
• Fluconazole (particularly for
meningitis)
Features of systemic fungal pathogens
Organism Culture at 25 0C Culture at 370C Tissue Primary Disseminate
disease d disease
C.neoformans Ecapsulated yeast Ecapsulated yeast Ecapsulated yeast pneunonia C. meningitis
H. Capsulatum Mold, tuberculate Small yeast Small intracellular Pneumonia, RES
macroconid yeast hilar enlargement
adenopthay
B. dermatitidis mold yeast Small yeast pneunonia Skin and
bone lesions
C. immitis Mold, spherules spherules Vally fever Pneumonia,
arthroconidia meningitis
Skin & bones
P. brasiliensis mold yeast yeast pneunonia Skin and
RES
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.
