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Medical Mycology Outline

1. 2. 3. 4. 5. Introduction, Actinomycetes Yeasts, Dermatophytes Filamentous Fungi, Dimorphic Fungi Dimorphic Fungi Opportunistic Fungi

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INTRODUCTION

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A. Classification

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What is a Fungus ?
Eukaryotic a true nucleus Do not contain chlorophyll Have cell walls Produce filamentous structures Produce spores
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Species of Fungi
100,000 200,000 species
About 300 pathogenic for man
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Kingdom Fungi
Ascomycota Basidiomycota Zygomycota Mitosporic Fungi
(Fungi Imperfecti)
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Eukaryocytes

KINGDOM

CHARACTERISTIC

EXAMPLE

Monera

Prokaryocyte

Bacteria Actinomyces Protozoa Fungi

Protista Fungi

Eukaryocyte Eukaryocyte * Eukaryocyte

Plants

Plants Moss
Arthropods Mammals Man

Animals

Eukaryocyte *

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KINGDOM

CHARACTERISTIC

EXAMPLE

Monera

Prokaryocyte

Bacteria Actinomyces Protozoa Fungi Plants Moss

Protista Fungi Plants

Eukaryocyte Eukaryocyte * Eukaryocyte

Animals

Eukaryocyte *

Arthropods Mammals
Man

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SIZE COMPARISON OF PATHOGENS


Cocci Bacilli Spirochetes Viruses Protozoa Nematodes Fungi 0.8 u 4-6 u 8 - 10 u 0.08 u 15 u 10 mm 10 15 u

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Actinomyces (True Bacteria)


Tradition Clinical infection resembles mycoses Actinomyces grow on mycotic media Actinomyces grow slowly (24-48 h) Gross colonies resemble fungi
(rough,heaped, short aerial filaments)

Resemble mycelia microscopically, with branched mycelia in tissue and smears.


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MYCOTIC DISEASES (Four Types)


1. Hypersensitivity
Allergy Production of toxin Pre-formed toxin

2. Mycotoxicosis 3. Mycetismus (mushroom poisoning) 4. Infection


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Hypersensitivity

FARMERS LUNG Moldy hay MALT WORKERS DISEASE Moldy barley CHEESE WASHERS LUNG Moldy cheese WOOD TRIMMERS DISEASE Moldy wood

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PATHOGENIC FUNGI

NORMAL HOST
Systemic pathogens - 25 species Cutaneous pathogens - 33 species Subcutaneous pathogens - 10 species

IMMUNOCOMPROMISED HOST
Opportunistic fungi - 300 species
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PARASITIC STATE
1. Increased metabolic state 2. Modified metabolic pathways 3. Modified cell wall structure
Carbohydrate content Lipid structure RNA aggregates

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PATHOGENICITY OF FUNGI
1. Thermotolerance
2. Ability to survive in tissue environment 3. Ability to withstand host defenses

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REVIVED INTEREST IN MYCOLOGY

1. 2. 3. 4. 5. 6. 7.

Increased frequency of mycotic diseases Increased awareness by physicians Better trained laboratory personnel More invasive procedures used on patients Increased use of immunosuppressive drugs Increase in immunosuppressive disease Better laboratory diagnostic tools
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B. MORPHOLOGY

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MORPHOLGY
Yeasts Hyphae (filamentous fungi, mycelium)
Septate Coenocytic (non-septate)

Dimorphic
Yeast Mycelium
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Dimorphic Fungi
Yeast Form
Parasitic form Tissue form Cultured at 37 C

Mycelial Form
Saprophytic form Cultured at 25 C
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SPORES
SEXUAL ASEXUAL
Arthrospore Blastospore Chamydospore Conidia
Microconidia Macroconidia
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C. EPIDEMIOLOGY

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ECOLOGICAL ASSOCIATION
PATHOGEN HUMAN SOIL _________________________________________ Blastomyces dermatitidis 1898 1964 Cryptococcus neoformans 1894 1951 Coccidioides immitis 1900 1932 Histoplasma capsulatum 1934 1949
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Mycotic Diseases Are NOT Contagious

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ESTABLISHMENT OF INFECTION WITH A MYCOTIC AGENT DEPENDS ON

1. Inoculum size 2. Resistance of the host


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THE CLINICIAN MUST DISTINGUISH BETWEEN: COLONIZATION FUNGEMIA

INFECTION
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PORTAL OF ENTRY
RESPIRATORY TRACT
MOUTH EYE

SKIN
HAIR NAILS RESPIRATORY TRACT GASTROINTESTINAL TRACT URINARY TRACT
SKIN

UROGENITAL TRACT
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ANUS

COLONIZATION
RESPIRATORY TRACT
MOUTH EYE

Multiplication of an organism at a given site without harm to the host


UROGENITAL TRACT
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SKIN

ANUS

INFECTION
RESPIRATORY TRACT
MOUTH EYE

Invasion and multiplication of organisms in body tissue resulting in local cellular injury.
UROGENITAL TRACT
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SKIN

ANUS

GEOGRAPHIC DISTRIBUTION
The present ease and frequency of world-wide travel make it more likely that physicians in the United States will be confronted with a variety of unfamiliar mycoses acquired in distant parts of the country or of the world.

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Endemic Mycoses
Those fungus infections with a limited geographic distribution. They are all caused by dimorphic fungi
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D. DIAGNOSIS

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Diagnosis 1. Wet Mount 2. Skin test 3. Serology 4. Fluorescent antibody 5. Biopsy and histopathology 6. Culture 7. DNA probes
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Diagnosis 1. Wet Mount 2. Skin test 3. Serology 4. Fluorescent antibody 5. Biopsy and histopathology 6. Culture 7. DNA probes
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DIRECT MICROSCOPIC OBSERVATION

10 % KOH Gentle Heat

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KOH Wet Mount

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Diagnosis 1. Wet Mount 2. Skin test 3. Serology 4. Fluorescent antibody 5. Biopsy and histopathology 6. Culture 7. DNA probes
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SKIN TESTING
(DERMAL HYPERSENSTIVITY)
Use is limited to :
Determine cellular defense mechanisms Epidemiologic studies

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Diagnosis 1. Wet Mount 2. Skin test 3. Serology 4. Fluorescent antibody 5. Biopsy and histopathology 6. Culture 7. DNA probes
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FUNGI ARE POOR ANTIGENS

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FUNGAL SEROLOGY ANTIBODIES


Latex Agglutination
Immunodiffusion Complement Fixation

IgM
IgG IgG

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DIRECT FLUORESCENT ANTIBODY


CAN BE APPLIED TO

1. HISTOLOGIC SECTIONS 2. CULTURE


Viable organisms Non-viable organisms
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INCUBATION TEMPERATURE
37 C - Body temperature 25 C - Room temperature

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E. TREATMENT

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THERAPY
Because they are eukaryotic, fungi are biochemically similar to the human host. Therefore it is difficult to develop chemotherapeutic agents that will destroy the invading fungus without harming the patient.

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A BASIC TENET OF PATHOLGY :

A CAUSE OF IRREVERSIBLE CELL INJURY IS CELL MEMBRANE DAMAGE.

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IN FUNGAL THERAPY

We attempt to induce cell injury by causing the cell membrane of the fungus to become permeable.

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PRIMARY ANTI-FUNGAL AGENTS


1. Polyene derivatives
Amphotericin B Nystatin Ketoconazole Fluconazole Itraconazole Voriconazole Posaconazole
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2. Azoles

AMPHOTERICIN B Mechanism of Action


Amphotericin B binds to sterols Ergosterol is a constituent of the fungal cell wall AMB has a greater avidity for ergosterol than for the cholesterol in the human cell wall Binding to the fungal cell wall alters the permeability and the intracellular contents leak

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AMPHOTERICIN B Disadvantages
Intravenous administration Thrombophlebitis Nephrotoxic Fever Chills Anemia Long term administration
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Azoles
There are a few rare serious side effects from Itraconazole and Fluconazole

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PRIMARY ANTI-FUNGAL AGENTS


3. Griseofulvin 4. 5-fluorocytosine (5-FC) 5. Allylamines -Terbinafine (Lamasil) 6. Echinocandins - Caspofungin
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Griseofulvin
A slow acting drug used for skin and nail infections. It accumulates in the stratum corneum and prevent hyphal penetration through these layers

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5-fluorocytosine

(5-FC)
Interferes With RNA Synthesis

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MECHANISMS OF ACTION
Polyenes
Azoles Griseofulvin

Ergosterol in cell membrane Interfere with ergosterol synthesis Forms a barrier to fungal growth
Inhibits RNA synthesis
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5 - FC

F. Clinical Classification of Mycoses


Cutaneous Subcutaneous Systemic Opportunistic

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Cutaneous Mycoses
Skin, hair and nails Rarely invade deeper tissue Dermatophytes

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Subcutaneous Mycoses
Confined to subcutaneous tissue and rarely spread systemically. The causative agents are soil organisms introduced into the extremities by trauma

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Systemic Mycoses
Involve skin and deep viscera May become widely disseminated Predilection for specific organs
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