Dental / Optometry Fundamentals II
Stephen A. Moser, Ph.D.
10/26/2011
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 Geography

Endemic mycoses

Worldwide mycoses
 Transmission of infection




Respiratory inhalation (systemic mycoses)
Cutaneous inoculation (sporotrichosis)
Systemic invasion by opportunistic normal flora
(candidiasis)
Contact with infected hosts (dermatophytoses)
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 Risk factors and manifestations of disease

True pathogens versus opportunists


Environmental risk factors for systemic fungal disease
• Location and travel
• Occupation
Host defenses and susceptibility to systemic fungal disease (CMI most important)
• Congenital and acquired T cell deficiencies (including
AIDS)
• Immunosuppression (transplants and malignancies)
• Diabetes mellitus
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Endemic Distribution for Blastomycosis
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 Aerobic - obligate or facultative
 Eukaryotic : membrane bound nucleus and cytoplasmic organelles (may be multinucleate)
 Achlorophyllous
 Morphology (unicellular or multicellular)
 Saprophytic (heterotrophic)
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 Cell wall : multilayered polysaccharide

Cellulose, glucans, mannans, chitin, polypeptides

Absence of teichoic acids, peptidoglycan, LPS
 Cell membrane

Phospholipid bilayer

Ergosterol (relate to chemotherapy)
 Cytoplasm - typical eukaryotic organelles
 Nucleus - either uninucleate or multinucleate
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 Capsule

Present in some species (e.G. Cryptococcus neoformans )

Amorphous polysaccharide coating

Functions and activities
 Antiphagocytic
 Antigenic
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 Growth forms

Yeast - unicellular fungi which reproduce by budding ( Cryptococcus )

Mold - hyphae (mycelium)
 Septate hyphae ( Aspergillus )
 Non-septate, coenocytic hyphae ( Mucor )

Pseudohyphae ( Candida albicans )

Thermal dimorphism
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Differences Between Bacteria and Fungi
PROPERTY FUNGI BACTERIA
Cell diameter
Nucleus
5-50 microns
Eukaryotic
1-5 microns prokaryotic absent Cytoplasmic organelles Present
Cell membrane sterols present (ergosterol)
Cell wall
Metabolism
Thermal dimorphism chitin, glucans, mannans, peptides
Mainly aerobes, facultative anaerobes
Common in many pathogenic species absent (except
Mycoplasma) teichoic acids, peptidoglycan, LPS obligate and facultative aerobes and anaerobes absent
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Examples of Yeast &
Pseudohyphae
Blastoconidia
Pseudohypha
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Blastomyces dermatitidis Thermal
Dimorphism
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Example of True Septate Hyphae
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 Conidia (spores) – asexual structures

Blastospores – formed by budding yeasts
( Blastomyces )



Chlamydospores – terminal or intercalary cells with thick walls ( Candida albicans )
Arthrospores – formed by fragmentation of hyphae ( Coccidioides immitis )
Sproangiospores – formed in sporangia by cleavage ( Rhizopus )
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 Ascomycetes : Aspergillus, Histoplasma ,
Blastomyces , Dermatophytes
 Basidiomycetes : Cryptococcus ,
Mushrooms
 Zygomycetes : Order Mucorales Mucor ,
Rhizopus
 Deuteromycetes (Fungi Imperfecti):
Sporothrix , Coccidioides, Candida
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TYPE
1. Superficial
2. Cutaneous
DISEASE
Pityriasis versicolor
Ringworm (Tinea)
Candidiasis
ORGANISM
Malassezia furfur
Trichophyton species
Candida albicans and others
3. Subcutaneous
4. Systemic
Sporotrichosis
Pathogenic Fungi
Histoplasmosis
Blastomycosis
Coccidioidomycosis
Paracoccidioidomycosis
Opportunistic Fungi
Aspergillosis
Cryptococcosis
Candidiasis
Zygomycosis
Sporothrix schenckii
Histoplasma capsulatum
Blastomyces dermatitidis
Coccidioides immitis
Paracoccidioides brasiliensis
Aspergillus fumigatus and others
Cryptococcus neoformans
Candida albicans and others
Mucor and Rhizopus species
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 Inhalation of spores – major factor
 Inoculation of spores into skin
 Disease by normal flora in compromised host (Candida)
 Hypersensitivity
 Contact with infected host
(Dermatophytes)
 Mycotoxins
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 Microscopic Examination of tissues and body fluids


Gram stain
Giemsa






India Ink
Potassium hydroxide (KOH) wet prep
Hematoxylin and Eosin stain
Periodic-Acid Schiff stain (PAS)
Gomori-Methenamine Silver stain (GMS)
Mucicarmine or Alcian Blue stain
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Staphylococcus
Candida
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KOH Prep - Broad-base Budding Yeast
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Mucicarmine Stain C. neoformans
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 Acute pyogenic abscess (Candida)
 Chronic granuloma formation
(Histoplasma)
 Chronic, localized dermal inflammation
(Dermatophytes)
 Mixed pyogenic and granulomatous inflammation (Blastomyces)
 Blood vessel invasion with thrombosis and infarction (Mucor, Aspergillus)
 Hypersensitivity without tissue reaction
(allergic bronchopulmonary aspergillosis)
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 Utilize Sabouraud agar with antibiotics
 Identification criteria

Temperature of growth

Rate of growth

Colonial and microscopic morphology

Sporulation pattern

Biochemical reactions (yeast)
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 Generally poor and not as useful as in other pathogens such as viruses and bacteria, with some exceptions.
 Cryptococcal antigen by latex agglutination: serum and CSF.
 Coccidioides - early IgM response is useful for identification of acute primary disease -
CSF IgG prognostic value.
 Skin tests for DTH - problems:


Cross-reactivity.
High positive rate in endemic areas.
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 Clinical manifestations





Mucosal
• Vaginitis
• Esophagitis
• Oral thrush
Cutaneous
Chronic mucocutaneous
Systemic
• Fungemia
• Hepato-spleenic
• Endophthalmitis
• Renal
Urinary tract
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Mucocutaneous
Candidiasis
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Candida sp. Tissue GMS Stain
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 Clinical manifestations

Pneumonia

Aspergilloma

Allergic bronchopulmonary

Disseminated multiorgan involvement
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Allergic Bronchopulmonary Aspergillosis
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CNS Aspergillosis
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 Clinical manifestations

Sinusitis

Rhinocerebral

Pulmonary

Renal
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Rhinocerebral
Mucormycosis in Diabetic
Ketoacidosis
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Postmortem – Rhinocerebral Mucormycosis
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Non-septate Branching Hyphae (PAS)
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 Clinical manifestations

Most cases mild or sub-clinical pulmonary disease
• Dissemination appears to be common

Pneumonia

Chronic progressive pulmonary (cavitary)

Histoplasmoma

Disseminated
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Histoplasmosis
– Calcified
Lesions
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Histoplasmosis – Bone Marrow
H. capsulatum
Histiocyte
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In vitro In vivo
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Presumed Ocular Histoplasmosis
 Thought to be a late stage of primary histoplasmosis.
 Causes abnormal blood vessels – scar tissue.
 Organism has not been found in eye.
 Treated with laser surgery.
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Risk Factors for Endogenous
Endophthalmitis
Candidia species Central venous lines, neutropenia, abdominal surgery, intravenous drug abuse, broad-spectrum antibiotics
Aspergillus species Neutropenia, endocarditis, intravenous drug abuse, pulmonary disease being treated with high dose steroids, organ and stem cell transplant.
H. capsulatum
C. immitis
B. dermatitidis
C. neoformans
May accompany disseminated disease
Fusarium species Neutopenia, intravenous drug abuse
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

FDA approved






Polyenes (Amphotericin B, lipid encapsulated forms)
Azoles (fluconazole, itraconazole, ketoconazole, voriconazole)
Echinocandin (Caspofungin, Micafungin, Anidulafungin)
Nucleoside derivatives (5-flurocytosine)
Allyamines (Terbinafine)
Microtubule disruption (Griseofulvin)
Investigational


Nikkomycins (chitin synthase inhibitors)
Echinocandin/pnemocandin/lipopeptide class (inhibit glycan synthesis)
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 Mode of Action

Binds to ergosterol, increases membrane permeability resulting in leakage of cytoplasmic components and cell death – Fungicidal
 Spectrum of Activity

Candida, Crypto, Aspergillus, Histo, Blasto, Cocci, etc
 Limitations

Nephrotoxicity
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 Mode of Action


Prevents ergosterol synthesis by inhibiting the C-14 demethylation step (cytochrome P-450 rx)
Fungistatic
 Spectrum of Activity

Candida, Crypto, Trichsporonosis, dermatophytes
 Limitations

Resistance in some Candida sp – krusei and glabrata

Not effective for non-dermatophyte moulds.
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 Mode of Action

Prevents synthesis of beta 1,3-glucan required for cell wall.

Fungistatic
 Spectrum of activity

Aspergillus, Candida

NOT effective against Cryptococcus, zygomycetes.
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Early Diagnosis of Invasive
Fungal Infections
•
•
•
•
Obstacles
Because of Immunosuppression typical signs and symptoms of infection are frequently absent
Few clinical features are uniquely specific for systemic fungal infection
Sputum and blood cultures are frequently negative
Invasive procedures
–
May be necessary for definitive diagnosis
–
Are often complicated in severely immunocompromised patient
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Early Diagnosis of Invasive
Fungal Infections (Continued)
Benefits
 Early diagnosis permits selection of a therapy of maximal effectiveness
 Early intervention with antifungal therapy may help decrease the high mortality rate associated with serious systemic mycoses
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 How fungi differ from bacteria
 The major fungal infections
 The epidemiology of fungal infections
 Pathology of fungal infections
 Mechanism of action of antifungal agents
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