1 A Introduction

Medical Mycology Outline

1. Introduction, Actinomycetes2. Yeasts, Dermatophytes3. Filamentous Fungi, Dimorphic Fungi4. Dimorphic Fungi5. Opportunistic Fungi

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INTRODUCTION

A. Classification

What is a Fungus ?

• Eukaryotic – a true nucleus

• Do not contain chlorophyll

• Have cell walls

• Produce filamentous structures

• Produce spores

Species of Fungi

• 100,000 – 200,000 species

• About 300 pathogenic for man

Kingdom Fungi Eukaryocytes

•Ascomycota

•Basidiomycota

•Zygomycota

•Mitosporic Fungi

(Fungi Imperfecti)

KINGDOM CHARACTERISTIC EXAMPLE

Monera Prokaryocyte BacteriaActinomyces

Protista Eukaryocyte Protozoa

Fungi Eukaryocyte * Fungi

Plants Eukaryocyte PlantsMoss

Animals Eukaryocyte * ArthropodsMammals

KINGDOM CHARACTERISTIC EXAMPLE

Monera Prokaryocyte BacteriaActinomyces

Protista Eukaryocyte Protozoa

Fungi Eukaryocyte * Fungi

Plants Eukaryocyte PlantsMoss

Animals Eukaryocyte * ArthropodsMammals

Cocci 0.8 u

Bacilli 4-6 u

Spirochetes 8 - 10 u

Viruses 0.08 u

Protozoa 15 u

Nematodes 10 mm

Fungi 10 – 15 u

SIZE COMPARISON OF PATHOGENS

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.

MYCOTIC DISEASES(Four Types)

1. Hypersensitivity– Allergy

2. Mycotoxicosis– Production of toxin

3. Mycetismus (mushroom poisoning)– Pre-formed toxin

4. Infection

Hypersensitivity

• FARMER’S LUNG – Moldy hay

• MALT WORKER’S DISEASE – Moldy barley

• CHEESE WASHER’S LUNG – Moldy cheese

• WOOD TRIMMER’S DISEASE – Moldy wood

PATHOGENIC FUNGI

• NORMAL HOST

• Systemic pathogens - 25 species• Cutaneous pathogens - 33 species• Subcutaneous pathogens - 10 species

• IMMUNOCOMPROMISED HOSTOpportunistic fungi - 300 species

PARASITIC STATE

1. Increased metabolic state

2. Modified metabolic pathways

3. Modified cell wall structure– Carbohydrate content– Lipid structure– RNA aggregates

PATHOGENICITY OF FUNGI

1. Thermotolerance

2. Ability to survive in tissue environment

3. Ability to withstand host defenses

REVIVED INTEREST IN MYCOLOGY

1. Increased frequency of mycotic diseases

2. Increased awareness by physicians

3. Better trained laboratory personnel

4. More invasive procedures used on patients

5. Increased use of immunosuppressive drugs

6. Increase in immunosuppressive disease

7. Better laboratory diagnostic toolswww.freelivedoctor.com

B. MORPHOLOGY

MORPHOLGY

• Yeasts

• Hyphae (filamentous fungi, mycelium)– Septate– Coenocytic (non-septate)

• Dimorphic– Yeast– Mycelium

Dimorphic Fungi• Yeast Form

• Parasitic form• Tissue form• Cultured at 37 C

• Mycelial Form• Saprophytic form• Cultured at 25 C

SPORES

• SEXUAL

• ASEXUAL– Arthrospore– Blastospore– Chamydospore– Conidia

• Microconidia

• Macroconidia

C. EPIDEMIOLOGY

ECOLOGICAL ASSOCIATION

PATHOGEN HUMAN SOIL

_________________________________________

Blastomyces dermatitidis 1898 1964

Cryptococcus neoformans 1894 1951

Coccidioides immitis 1900 1932

Histoplasma capsulatum 1934 1949

Mycotic Diseases Are NOTContagious

ESTABLISHMENT OF INFECTION WITH A MYCOTIC AGENT DEPENDS ON

1. Inoculum size

2. Resistance of the host

THE CLINICIAN MUST DISTINGUISH BETWEEN:

• COLONIZATION

• FUNGEMIA

• INFECTION

UROGENITAL TRACT

MOUTHRESPIRATORY TRACT

PORTAL OF ENTRY

•SKIN

•HAIR

•NAILS

•RESPIRATORY TRACT

•GASTROINTESTINAL TRACT

•URINARY TRACT

UROGENITAL TRACT

COLONIZATION

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

UROGENITAL TRACT

INFECTION

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

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.

Endemic Mycoses

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

D. DIAGNOSIS

Diagnosis

1. Wet Mount2. Skin test3. Serology4. Fluorescent antibody5. Biopsy and histopathology6. Culture7. DNA probes

Diagnosis

DIRECT MICROSCOPIC OBSERVATION

• 10 % KOH

• Gentle Heat

KOH Wet Mount

Diagnosis

SKIN TESTING(DERMAL HYPERSENSTIVITY)

Use is limited to :

– Determine cellular defense mechanisms– Epidemiologic studies

Diagnosis

FUNGI ARE POOR ANTIGENS

FUNGAL SEROLOGYANTIBODIES

• Latex Agglutination IgM

• Immunodiffusion IgG

• Complement Fixation IgG

DIRECT FLUORESCENT ANTIBODYCAN BE APPLIED TO

1. HISTOLOGIC SECTIONS

2. CULTURE

• Viable organisms• Non-viable organisms

INCUBATION TEMPERATURE

• 37 C - Body temperature

• 25 C - Room temperature

E. TREATMENT

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.

A BASIC TENET OF PATHOLGY :

A CAUSE OF IRREVERSIBLE CELL INJURY IS CELL MEMBRANE DAMAGE.

IN FUNGAL THERAPY

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

PRIMARY ANTI-FUNGAL AGENTS

1. Polyene derivatives– Amphotericin B

– Nystatin

2. Azoles– Ketoconazole

– Fluconazole

– Itraconazole

– Voriconazole

– Posaconazole

AMPHOTERICIN BMechanism 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

AMPHOTERICIN BDisadvantages

• Intravenous administration

• Thrombophlebitis

• Nephrotoxic

• Fever

• Chills

• Anemia

• Long term administrationwww.freelivedoctor.com

Azoles

There are a few rare serious side effects from Itraconazole and Fluconazole

PRIMARY ANTI-FUNGAL AGENTS

3. Griseofulvin

4. 5-fluorocytosine (5-FC)

5. Allylamines

-Terbinafine (Lamasil)

6. Echinocandins

- Caspofungin

Griseofulvin

A slow acting drug used for skin and nail infections. It accumulates in the stratum corneum and prevent hyphal penetration through these layers

5-fluorocytosine(5-FC)

Interferes With RNA Synthesis

MECHANISMS OF ACTION

• Polyenes

• Azoles

• Griseofulvin

• 5 - FC

• Ergosterol in cell membrane

• Interfere with ergosterol synthesis

• Forms a barrier to fungal growth

• Inhibits RNA synthesis

F. Clinical Classification of Mycoses

•Cutaneous

•Subcutaneous

•Systemic

•Opportunistic

Cutaneous Mycoses

Skin, hair and nails

Rarely invade deeper tissue

Dermatophytes

Subcutaneous Mycoses

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

Systemic Mycoses

• Involve skin and deep viscera

• May become widely disseminated

• Predilection for specific organs

1 A Introduction

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