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

Man


KINGDOM CHARACTERISTIC EXAMPLE

Monera Prokaryocyte BacteriaActinomyces

Protista Eukaryocyte Protozoa

Fungi Eukaryocyte * Fungi

Plants Eukaryocyte PlantsMoss

Animals Eukaryocyte * ArthropodsMammals

Man


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


EYE

SKIN

UROGENITAL TRACT

ANUS

MOUTHRESPIRATORY TRACT

PORTAL OF ENTRY

•SKIN

•HAIR

•NAILS

•RESPIRATORY TRACT

•GASTROINTESTINAL TRACT

•URINARY TRACT


EYE

SKIN

UROGENITAL TRACT

ANUS


COLONIZATION

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


EYE

SKIN

UROGENITAL TRACT

ANUS


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


Documents

1 A Introduction