Fungal infections : Cutaneous mycoses Subcutaneous mycoses Systemic mycoses: Originate in lung  spread to other organs Opportunistic mycoses: Cause opportunistic infections

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Fungal infections
Med_students0

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Classification
1. Cutaneous mycoses
2. Subcutaneous mycoses
3. Systemic mycoses:
– Originate in lung  spread to other
organs
4. Opportunistic mycoses:
• Cause opportunistic infections

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SUBCUTANEOUS MYCOSES
Sporotrichosis

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SUBCUTANEOUS MYCOSES
• caused by fungi that grow in soil and on vegetation
and are introduced into subcutaneous tissue through
trauma.
• Example: Sporothrix schenckii
• Diseases: Sporotrichosis
• Characteristics:
– Fungus lives on vegetation.
– Introduced into s.c tissue  Trauma to the skin,
typically by a thorn.
• Pathology:
– Local pustule or ulcer with nodules along the draining
lymphatics.

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Systemic fungal infections
• Four fungi that cause systemic diseases:
1. Histoplasma capsulatum
2. Blastomyces dermatidis
3. Coccidioides immitis
4. Paracoccidioides brasiliensis
– All are dimorphic fungi****
– Mold form at 25 0C
– Yeast form at 37 0C
– “(mold in cold, yeast in heat)”
– All acquired by inhalation of spores

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Histoplasma capsulatum yeast forms in macrophages

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Tree Bark appearance :Histoplasma granuloma of
the lung.

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Blastomycosis
Broad-based Budding

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Coccioidomycosis spherule in tissue
Spherule
Endospores

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Systemic fungal infections
Organism Coccidiodes Histoplasma Blastomyces
Disease Self limited
pneumonia
Self limited
pneumonia
Self limited
pneumonia
Geography Arizona,
Central
valley of
California
Tennessee,
Ohio and
Mississippi
valleys
Mississippi,
Ohio and
Missouri
valleys
Soil type Dry soil Bat or bird
excreta
Dead-
decomposing
wood

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Histoplasma capsulatum
• An intracellular fungus that infects macrophages.
• Causes: Histoplasmosis
– Most common systemic fungal infection.
– Acquired by inhalation of spores from dust
particles contaminated with bird droppings.
• Associated with bats, birds and cave
exploration.
• Caves – “Spelunker’s disease”
• S/S: Chills, fever. Cough, headache and
pneumonia.
– Produces granulomatous inflammation with
calcification ( tree bark appearance).

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Histoplasma capsulatum
• Endemic areas in US:
– Midwest (Ohio and Mississippi river
valleys)***
• Morphology
– Yeast forms in macrophages****

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Histoplasma capsulatum yeast forms in macrophages

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Tree Bark appearance :Histoplasma granuloma of
the lung.

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Blastomyces dermatitidis
• Causes = Blastomycosis
• Two major clinical forms ( mostly occurs in
males)
1.Pulmonary blastomycosis
2.Cutaneous blastomycosis
• Endemic areas:
– Great Lake region, Central US, South eastern
US
• Found in moist soil with decomposing wood
• Morphology:
– Organism in tissue exhibits broad-based
budding

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Blastomycosis
Broad-based Budding

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Coccidioides immitis
• Causes: Coccidioidomycosis
• Acquired by inhaling arthrospores in dust** in
the Southwest or San Joaquin valley in
California.(= San Joaquin Valley fever).
• Increased incidence after earthquakes.
• Presents with flu like symptoms
– Cough, fever, arthralgia and rash
• Morphology:
– Tissue form is SPHERULE
– Filled with small endospores.

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Coccioidomycosis spherule in tissue
Spherule
Endospores

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Paracoccidoides brasiliensis
• Causes – Paracoccidioidomycosis
• Range – Central and South America
• Clinical manifestation: similar to Histo and blasto
but with predilection to cause oral and nasal
lesions****
• Morphology:multiple buds, like a ship’s wheel****
Paracoccidioidomycosis
(ship’s wheel)
Tongue lesion

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Opportunistic Mycoses
AIDS and Immunosuppression have
increased the incidence of
opportunistic fungal infections a
hundred fold

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Opportunistic Mycoses
• Most common species
– Cryptococcus neoformans
– Candida albicans
– Aspergillus
– Zygomycetes
• Muror, Rhizopus,Absidia
– Pneumocystis carinii
– Penicillium marnefeii

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• Causes: Cryptococcosis
• MC fungal opportunistic infection in
immunocompromised hosts.
 MC fungal cause of Meningitis In AIDS
• Infection occurs due to inhalation.
• Contracted from living or working near pigeon
excreta.****
– Aka “Pigeon Handlers Disease”
Cryptococcus neoformans

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Cryptococcus neoformans
Morphology
• Not a dimorphic fungi
• It has only yeast form and no pseudohyphal or
hyphal forms.
– Budding yeast with **narrow based buds***.
– Thick gelatinous capsule**.
• Stains red with PAS and Mucicarmine.
• India ink preparation: gives a negative image ;
does not stain the fungus.****

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Cryptococcus neoformans:
Numerous organisms with large mucoid capsule

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Cryptococcosis of lung in patient with AIDS.
Mucicarmine stain.

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India ink preparation of cerebrospinal fluid in a patient
with Cryptococcus neoformans meningitis

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Candidiasis
Candida albicans

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Candida albicans
• Normal flora: mouth, GI, vagina
– in balance with other flora
• Infections due to flora imbalance
– broad spectrum antibiotics, corticosteroids,
diabetes mellitus, HIV
• Infections:
– Superficial lesions to disseminated infections.
• Superficial candidiasis:
– More often in Diabetics and burn patients.
• Disseminated candidiasis associated with:
– immunosuppression and neutropenia.

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Superficial Candida infections
• Oral thrush: Chr.by gray white dirty looking
pseudomembrane composed of matted organisms
and inflammatory debris.
• Seen in : Newborns, patients on oral steroids, and
broad spectrum antibiotics , HIV positive patients.

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Oral thrush. CDC

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Superficial Candida infections
• Candida Esophagitis: Seen in:
– AIDS
– Patients with hematological
malignancies
– Presents with dysphagia and
retrosternal pain
– Endoscopy: white plaques
and pseudo membrane on
esophageal mucosa.
Severe candidiasis of the
esophagus

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• Candida vaginitis:
– Women who are:
• Diabetic, pregnant or on OC pills
• Associated with intense itching and curd like
discharge.
• Cutaneous Candidiasis: Can present in many different
forms.
– Infection of
• Nails = Onychomycosis
• Intertriginous skin : intertrigo
• Penile skin : balanitis
• Perineum of infants : Diaper rash
Superficial Candida infections

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Superficial Candida infections
Diaper rash
Intertrigo
Candida vaginitis
Balanitis

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Invasive Candidiasis
• Due to blood borne dissemination of the fungus.
• Can result in:
– Renal abscess
– Myocardial abscess and endocarditis
• Most common fungal cause of endocarditis in
prosthetic heart valves and IVDA**.
– Brain involvement:
• Meningitis
• Parenchymal abscess
• Occurs most commonly in patients with leukemia
undergoing treatment.

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Morphology
• In tissue sections candida can appear as:
– Yeast forms
– Pseudohyphae
• Pseudohyphae : imp diagnostic clue
– Budding yeast cells joined end to end.
• Can be seen with:
– Routine H & E stain
– Fungal stains:
• Gomori methenamine silver
• PAS

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Characteristic pseudohyphae and budding yeast of
Candida.

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Candida albicans methenamine silver stain. Pseudohyphae and budding yeast .
ASCP

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With a PAS stain, the budding cells and pseudohyphae (short
filaments that are not true hyphae) of Candida stain bright
red.

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Aspergillus fumigatus
• most common species to cause Aspergillosis
• Predisposing Factors:
– Neutropenia and corticosteroid use
• Three Forms Of Disease:
1. Colonizing aspergillosis= (aspergilloma)
– fungal ball that develop in a preexisting cavity
tubercular cavity (in lung)
– Can cause massive hemoptysis
2. Invasive aspergillosis: vessel invasion
– Can cause hemorrhagic infarctions
3. Allergic bronchopulmonary aspergillosis
– Due to development of hypersensitivity to the
fungus.
– Characterized by increased IgE ** levels and
eosinophilia

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Morphology
• Aspergillus Aspergillus forms
– Fruiting bodies and
– Septate hyphae ****
– Narrow angle ,regular branching (at 45
degree angles)****

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Aspergilloma
Fungus ball in a dilated bronchus

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Branching Aspergillus hyphae

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Septate hyphae with acute-angle branching

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GMS stain, show septate hyphae with acute-angle
branching. Occasionally, Aspergillus may
demonstrate fruiting bodies (inset)

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Mucormycosis (zygomycosis)
• Cause: Bread mold fungi including:
• Rhizopus, Absidia and Mucor
• Result in opportunistic infections in
immunosuppressed patients.
• Predisposing factors:
– Neutropenia, corticosteroid use, diabetes
mellitus.
• Rhinocerebral mucormycosis
– Most common (seen in diabetics)
– Infection originates in Para-nasal sinuses 
ocular orbit brain.
• Non-septate broad hyphae with irregular
branching***

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Rhinocerebral Mucormycosis
Extensive involvement of the orbit

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The broad, non-septate hyphae seen here are
characteristic for Mucor.

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Vessel invading fungi
• Can cause infarction
– RAM= Rhizopus, Aspergillus and Mucor
are angioinvasive

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Pneumocystis carinii
• Causes an interstitial pneumonitis with
severe hypoxemia.
• Is the MC initial infection in AIDS.
• Occurs when CD 4 counts fall below 200**
cells/ul
• Produces a foamy alveolar exudate (cotton
candy exudate) and
• Diffuse alveolar and interstitial infiltrate
on X ray
• Best seen with silver and Giemsa stain

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The exudate consists of edema fluid, protein,
Pneumocystis organisms, and dead
macrophages.

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Gomori methenamine silver (GMS) stain- the organisms appear
as crushed ping-pong balls, or crescent shapes, or folded
spheres, or....

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A silver stain of P. carinii cysts from lung tissue showing the
typical 'deflated ball' shape.

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1. A 39 year old HIV positive woman is in severe
respiratory distress with fever and chills. A lung
biopsy was performed and a fungus was seen
which has septate hyphae which branches acutely
(45 angle). What is the fungus responsible for
this patient’s symptoms?
A. Cryptococcus neoformans
B. Aspergillus fumigatus
C. Histoplasma capsulatum
D. Blastomyces dermatitidis
E. Coccidioides immitis.

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Which of the following fungi is associated with
skin lesions occurring frequently on moisture-
damaged skin? Disseminated infection also occurs
in immunosuppressed patients and intravenous
drug users.
A. Cryptococcus neoformans
B. Histoplasma capsulatum
C. Candida albicans
D. Blastomyces dermatitidis
E. Coccidioides immitis

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A 27 years old intravenous drug user presents with
difficulty swallowing. Examination of the
oropharynx reveals white plaques (thrush). Which of
the following is BEST description of the microscopic
appearance of the microorganism responsible for
this patients iliness?
(A) Sepherules
(B) Mold with nonseptate hyphae
(C) Mold with septate hyphae
(D) Encapsulated yeast
(E) Budding yeasts and pseudohyphae

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Your patient is a 45-year-old woman. This morning,
she awoke with a pain near her right eye. On
physical examination, her temperature is 38 C and
the skin near her eye is necrotic. A biopsy specimen
of the lesion contains nonseptate hyphae invading
the blood vessels. Of the following, which one is
the MOST likely cause?
(A) Histoplasma capsulatum
(B) Aspergillus fumigatus
(C) Cryptococcus neoformans
(D) Mucor species

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A 48 year old immunocompromised man is seen in the
emergency. A lumbar puncture was performed which
showed an encapsulated spherical fungal cell when
isolated using an India Ink stain. Which of the
following fungus is responsible for this patient’s
symptoms?
A. Cryptococcus neoformans
B. Candida albicans
C. Histoplasma capsulatum
D. Blastomyces dermatitidis
E. Coccidioides immitis