Medical Mycology
Prof. Khaled H. Abu-Elteen
Zarqa Private UniversityBiology
4223 – The Fungi
Fungal Diseases
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Mycosis- fungal infection
 < 100 cause human disease
 Not highly contagious
 Humans acquire from nature
Groups based on degree on tissue involvement
and mode of entry
Cutaneous mycoses-dermatophytes
 Epidermis, hair & nails
 Contagious-direct or indirect contact
 Secrete keratinase that degrades keratin
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4223 – The Fungi
Cutaneous Mycoses
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Tinea( worm) capitis –blisters with scaly ring
Ringworm of the scalp
 Spreads circularly forming bald spots
 Spread by contact with fomites , cats and
dogs
Tinea cruris- ringworm of groin
Tinea pedis - athlete's foot
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4223 – The Fungi
Systemic Mycoses
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Dimorphic fungi
 Yeast form is invasive
Can spread throughout body
Usually caused by fungi in soil
Inhalation of spores
Begins in lungs and spread to rest of
body
Not contagious person to person
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4223 – The Fungi
Introduction
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Obligate Parasitic Fungi
(dermatophytes): evolved to attack the
outer surface of humans
Facultative soil fungi: thermal
dimorphic saprobes, adaptations to
human body
Opportunistic saprobes: attack people
with compromised immune systems
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4223 – The Fungi
Introduction
Fungal Infections
 Superficial infections: involve outermost
layers of skin and its appendages [ nails or
hair] ( Dermatophytosis)
 Cutaneous infections: involve deeper layers
of skin causing allergic or inflammatory
response
 Subcutaneous infections: fungi with low
virulence, localized infection, or spread by
mycelial growth
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4223 – The Fungi
Introduction

Systemic infections: caused by true
pathogenic fungi or opportunistic
saprobes
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4223 – The Fungi
Mycoses: diseases cause by
fungi
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Superficial
Subcutaneous
Opportunistic
Cutaneous
Systemic
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4223 – The Fungi
The Situation
Frequency
- most common fungal pathogen worldwide
- 4th leading causes of nosocomial infections, 40% mortality
- significant mortality and morbidity in low birth-weight infants
- affects 75% women, 45% experience recurrence
> 10 million visits/year
- classified as a STD by CDC
Immunocompromised
- cancer and HIV-AIDs patientsC
- most commonly manifested in patients with leukemia
or HIV-AIDs infections. Oral candidiasis is often a
clue to acute primary infectionC
Public Concerns
- increasing resistance to drug therapies due to antibiotics and
antifungals
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4223 – The Fungi
FUNGAL DISEASES
Mycosis: Any fungal disease. Tend to be chronic because fungi
grow slowly.
Mycoses are classified into the following categories:
I. Systemic mycoses: Fungal infections deep within the body.
Can affect a number if tissues and organs.
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Usually caused by fungi that live in the soil and are inhaled.
Not contagious.
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Examples:
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Histoplasmosis (Histoplasma capsulatum): Initial
infection in lungs. Later spreads through blood
to most organs.
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Coccidiomycosis (Coccidioides immites):
Resembles tuberculosis.
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4223 – The Fungi
Systemic Mycosis: Histoplasmosis
Disseminated Histoplasma capsulatum, lung infection.
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4223 – The Fungi
FUNGAL DISEASES (Continued)
II. Cutaneous mycoses: Fungal infections of the skin, hair, and
nails.
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Secrete keratinase, an enzyme that degrades keratin.
Infection is transmitted by direct contact or contact with
infected hair (hair salon) or cells (nail files, shower floors).
Examples:
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Ringworm (Tinea capitis and T. corporis)
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Athlete’s foot (Tinea pedis)
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Jock itch (Tinea cruris)
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4223 – The Fungi
Opportunistic Infection by Candida
albicans in an AIDS Patient
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4223 – The Fungi
Severe nail infection with Trichophyton rubrum in
a 37-year-old male AIDS patient.
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4223 – The Fungi
Disseminated Histoplasma capsulatum, skin infection.
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4223 – The Fungi
Cutaneous Mycosis
Ringworm skin infection: Tinea corporis
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4223 – The Fungi
Cutaneous Mycosis
Candida albicans
infection
of the nails.
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4223 – The Fungi
FUNGAL DISEASES (Continued)
III. Subcutaneous mycoses: Fungal infections beneath the
skin.
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Caused by saprophytic fungi that live in soil or on vegetation.
Infection occurs by implantation of spores or mycelial
fragments into a skin wound.
Can spread to lymph vessels.
IV. Superficial mycoses: Infections of hair shafts and
superficial epidermal cells. Prevalent in tropical climates.
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4223 – The Fungi
FUNGAL DISEASES (Continued)
Opportunistic mycoses: Caused by organisms that are
generally harmless unless individual has weakened defenses:
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AIDS and cancer patients
Individuals treated with broad spectrum
antibiotics
Very old or very young individuals (newborns).
Examples:
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Aspergillosis: Inhalation of Aspergillus spores.
Yeast Infections or Candidiasis: Caused mainly
by Candida albicans. Part of normal mouth,
esophagus, and vaginal flora.
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4223 – The Fungi
Cutaneous Infections
Dermatophytic hyphomycetes
 40 species
 Epidermophyton (2 species)
 Microsporum (17 species)
 Trichophyton (24 species)
 50% of dermatophytes human specific
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4223 – The Fungi
Cutaneous Infections
Cause common tinea (ringworm)
 Grow only on humans
 Reservoir not in soil or animals
 Reservoir in carpets and upholstery
for up to two years
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4223 – The Fungi
Cutaneous Infections
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Trichophyton
rubrum
Chronic infections
of the toe nails
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4223 – The Fungi
Tinea corporis
Subcutaneous mycoses
Subcutaneous infections - over 35
species produce chronic inflammatory
disease of subcutaneous tissues and
lymphatics. e.g. sporotrichosis ulcerated lesions at site of inoculation
followed by multiple nodules - caused
by a dimorphic fungus: Sporotrix
schenckii.
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4223 – The Fungi
Cutaneous Infections

Microsporum canis
 Reservoir in cat
 May move to humans or dogs
 Dies out after one or two personperson transfers
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4223 – The Fungi
Cutaneous Infections
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Disease process
 Fungus stimulates epithelial cells of
skin to divide more frequently
 Makes more keratin available to
fungus
 Some species race specific in humans
 Some species body location specific
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4223 – The Fungi
Cutaneous Infections

Candida albicans – candidiasis
 Normal component of gut mycota
 Excessive wetness  overgrowth on
skin
 Vaginal candidiasis common in
pregnant women
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4223 – The Fungi
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4223 – The Fungi
Biology of Candida albicans
Commensal
Pathogen
A thin-walled dimorphic fungus
Morphogenesis
Unicellular yeast (harmeless)
Filamentous (pathogenic)
Principal Cell Wall Polymers
Gluccan
Mannan
Figure 1. Yeast in Oral Scraping
A sample of an oral scraping contains yeast cells and
pseudohyphae
(www.doctorfungus.org)
Strict aerobe, favors moist surfaces
Commensally found in gut, genitals, and lungs
Body Temp 37º C, neutral pH
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4223 – The Fungi
Rapid Multiplication & Spread
Diseases by C. albicans
Thrush
Esophagitis
Cutaneous Candidiasis
Genital Yeast Infections
Deep Candidiasis
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4223 – The Fungi
Oropharyngeal Thrush
* Pseudomembranous
* Atrophic
* Angular chelitis
Figure 1. Angular chelitis
Symptoms
Risk Factors
HIV
Treatment: topical
antifungals
Figure 2. Oral Thrush, atrophic
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4223 – The Fungi
Figure 3. Oral Thrush, pseudomembranous
Genital Yeast Candidiasis
Symptoms
Risk Factors
- disruption of normal
microbiota
Figure 1. Vaginal Yeast Culture
Treatment
- direct genital administration
- tablets, suppositories, creams
Figure 2. Plasma cell balanitis. A
band-like infiltrate of plasma cells is in
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4223 – The Fungi
Deep Candidiasis
Figure 1. Four forms of invasive candidiasis
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4223 – The Fungi
Pathogenesis
Host Recognition
Adhesins
Enzymes
Hydrolases: Phosphoplipases, Lipases, Proteinases
Morphogenesis
Yeast form to Filamentous hyphae/pseudohyphae
Phenotypic Switching
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4223 – The Fungi
Virulence assay of different C. albicans strains using the skin equivalent (AST 2000)
Figure 1. skin equivalent before infection
Figure 2. Infection with pathogenic clinical isolate of C. albicans.
After 48 h the yeast penetrates the skin equivalent and destroys
the tissue
Figure 3. Infection with non-pathogenic C. albicans. This strain is not
able to penetrate into the tissue and thus behaves as avirulent as shown
in the mouse model of systemic infection.
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4223 – The Fungi
(Fraunhofer, 2002)
MORPHOGENESIS
Figure 1. Morphogenesis.
Morphogenesis in
C. albicans is a pivotal
virulence factor that allows
rapid multiplication and
subsequent dissemination
in host tissue.
(www.kent.ac.uk)
Figure 2. Morphogenic forms of Candida albicans
http://cbr-rbc.nrc-cnrc.gc.ca/thomaslab/candida/caindex.html
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4223 – The Fungi
Subcutaneous Infections
Fungal Activity
 Fungi normally saprobic
 Introduced through wounds
 Adapt to the human animal by changes in
 morphology
 physiology
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4223 – The Fungi
Subcutaneous Infections
Chromoblastosis
 Common among barefoot peoples of the
tropics
 Soil hyphomycete species
 Enters human by thorns or wood slivers
 Fungus grows  host cells respond by
rapid cell division  wart-like growths
on feet or legs
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4223 – The Fungi
Subcutaneous Infections
Mycotic Mycetoma
 Disease of barefoot tropical people
 Entry: wound on foot
 Attacks various tissues
 Stimulates formation of tumor
 Compact fungal colonies form within
tumor
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4223 – The Fungi
Subcutaneous Infections
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Skin ruptures and
some colonies
extrude
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4223 – The Fungi
Systemic Mycoses
Introduction
 Caused by . . .
 Specialized pathogens
 Dimorphic
 One form outside the host
 Another form inside the host
 Opportunistic saprobes
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4223 – The Fungi
Systemic Mycoses
Dimorphic Pathogen Mycoses
 Histoplasmosis
 Histoplasma capsulatum
 Grows on bird droppings, chicken
manure, bat guano
 Conidia inhaled  primary lung
infection  almost always fatal until
recently
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4223 – The Fungi
Systemic Mycoses

Histoplasma
capsulatum
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4223 – The Fungi
Systemic Mycoses
Coddidioidomycosis
 Coccidioides immitis
 Dry, saline soils
 Endemic to SW deserts of North
America
 Valley fever
 Until recently – almost always fatal
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4223 – The Fungi
Systemic Mycoses
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Infection, disease process, and clinical
symptoms similar to histoplasmosis
Can be effectively treated with
fluconazole
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4223 – The Fungi
Opportunistic Pathogens/Disease
General
 Pathogens all grow well at 37C
 None cause disease in well individuals
 Require breakdown in resistance system
 Complication of diabetes, AIDS,
advanced cancer, sequel to steroid or
antibiotic treatments
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4223 – The Fungi
Opportunistic Pathogens/Disease
Zygomycosis
 Species of Zygomycota
 Rhizopus, Mucor, Rhizomucor
 Rhinocerebral mycosis
 Spores enter through sinuses
 Grows rapidly outward to the eyes and
inward towards the brain
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4223 – The Fungi
Opportunistic Pathogens/Disease
Aspergillosis
 Aspergillus sp.
 Bronchiopulmonary aspergillosis
 Mucus within the bronchi  severe
allergic reaction
 Aspergilloma
 Forms a mycelia ball in lung cavity
formed from earlier TB
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4223 – The Fungi
Opportunistic Pathogens/Disease
Surgical intervention often required
Invasive aspergillosis
 Severely debilitated
 Immunosuppressed (AIDS)
Almost always fatal until recently
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4223 – The Fungi
AIDS and Mycoses
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Aspergillosis
Candidiases (Candidiasis seen in 2/3 of
AIDS patients
Cryptococcosis
Zygomycosis
Esophogeal candidiasis and
cryptococcosis are strong indicators of
AIDS
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4223 – The Fungi
PRIMARY ANTI-FUNGAL
AGENTS
1.
2.
Polyene derivatives
 Amphotericin B
 Nystatin
Azoles
 Ketoconazole
 Fluconazole
 Itraconazole
 Voriconazole
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4223 – The Fungi
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4223 – The Fungi
Azoles
There are a few rare
serious side effects
from Itraconazole and
Fluconazole
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4223 – The Fungi
5-fluorocytosine
(5-FC)
Interferes With RNA
Synthesis
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4223 – The Fungi
MECHANISMS OF ACTION
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Polyenes
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Azoles
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Griseofulvin
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5 - FC
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Ergosterol in cell
membrane
Interfere with
ergosterol synthesis
Forms a barrier to
fungal growth
Inhibits RNA
synthesis
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4223 – The Fungi