Medical Mycology

Medical Mycology
Prof. Khaled H. Abu-Elteen
Zarqa Private UniversityBiology

4223 – The Fungi
Fungal Diseases
 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

4223 – The Fungi
Cutaneous Mycoses
 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

4223 – The Fungi
Systemic Mycoses
 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
4223 – The Fungi
Introduction
 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

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
4223 – The Fungi
Introduction
 Systemic infections: caused by true

pathogenic fungi or opportunistic
saprobes

4223 – The Fungi
Mycoses: diseases cause by
fungi
 Superficial Cutaneous
 Subcutaneous Systemic
 Opportunistic

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 birthweight infants
affects 75% women, 45% experience recurrence
> 10 million visits/year
classified as a STD by CDC
Immunocompromised
cancer and HIVAIDs patientsC
most commonly manifested in patients with leukemia
or HIVAIDs infections. Oral candidiasis is often a
clue to acute primary infectionC
Public Concerns
increasing resistance to drug therapies due to antibiotics and
antifungals 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.
 Usually caused by fungi that live in the soil and are inhaled.
Not contagious.
 Examples:
 Histoplasmosis (Histoplasma capsulatum): Initial
infection in lungs. Later spreads through blood
to most organs.
 Coccidiomycosis (Coccidioides immites):
Resembles tuberculosis.
4223 – The Fungi
Systemic Mycosis: Histoplasmosis
Disseminated Histoplasma capsulatum, lung infection.

4223 – The Fungi
FUNGAL DISEASES (Continued)
II. Cutaneous mycoses: Fungal infections of the skin, hair, and
nails.
 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:
 Ringworm (Tinea capitis and T. corporis)
 Athlete’s foot (Tinea pedis)
 Jock itch (Tinea cruris)

4223 – The Fungi
Opportunistic Infection by Candida
albicans in an AIDS Patient

4223 – The Fungi
Severe nail infection with Trichophyton rubrum in
a 37-year-old male AIDS patient.
4223 – The Fungi
Disseminated Histoplasma capsulatum, skin infection.
4223 – The Fungi
Cutaneous Mycosis
Ringworm skin infection: Tinea corporis

4223 – The Fungi
Cutaneous Mycosis
Candida albicans infection

Zarqa Private of the
UniversityBiology
4223 – The Fungi
nails.
III. Subcutaneous mycoses: Fungal infections beneath the
skin.
 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 .

4223 – The Fungi
Opportunistic mycoses: Caused by organisms that are
generally harmless unless individual has weakened defenses:
 AIDS and cancer patients
 Individuals treated with broad spectrum
antibiotics
 Very old or very young individuals (newborns).
 Examples:
 Aspergillosis: Inhalation of Aspergillus spores.
 Yeast Infections or Candidiasis: Caused mainly
by Candida albicans. Part of normal mouth,
esophagus, and vaginal flora.
4223 – The Fungi
Cutaneous Infections
Dermatophytic hyphomycetes
 40 species
 Epidermophyton (2 species)
 Microsporum (17 species)
 Trichophyton (24 species)
 50% of dermatophytes human specific

4223 – The Fungi
 Cause common tinea (ringworm)

 Grow only on humans
 Reservoir not in soil or animals
 Reservoir in carpets and upholstery
for up to two years

4223 – The Fungi
 Trichophyton
rubrum
 Chronic infections
of the toe nails

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.

4223 – The Fungi
 Microsporum canis
 Reservoir in cat
 May move to humans or dogs
 Dies out after one or two person-
person transfers

4223 – The Fungi
 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

4223 – The Fungi
 Candida albicans – candidiasis

 Normal component of gut mycota
 Excessive wetness  overgrowth on
skin
 Vaginal candidiasis common in
pregnant women

4223 – The Fungi
4223 – The Fungi
Biology of Candida albicans
Commensal Pathogen
A thinwalled dimorphic fungus
Morphogenesis
Unicellular yeast (harmeless)
Filamentous (pathogenic)
Principal Cell Wall Polymers
Gluccan Figure 1. Yeast in Oral Scraping
Mannan 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
Rapid Multiplication & Spread 4223 – The Fungi
Diseases by C. albicans
Thrush
Esophagitis
Cutaneous Candidiasis
Genital Yeast Infections
Deep Candidiasis

4223 – The Fungi
Oropharyngeal Thrush
* Pseudomembranous
* Atrophic
* Angular chelitis
Figure 1. Angular chelitis
Symptoms
Risk Factors
HIV
Treatment: topical
antifungals Figure 3. Oral Thrush, pseudomembranous
Figure 2. Oral Thrush, atrophic

4223 – The Fungi
Genital Yeast Candidiasis
Symptoms
Risk Factors Figure 1. Vaginal Yeast Culture
disruption of normal
microbiota
Treatment
direct genital administration
tablets, suppositories, creams
Figure 2. Plasma cell balanitis. A
bandlike infiltrate of plasma cells is in
Zarqa Private UniversityBiology the dermis of the male penis.
4223 – The Fungi
Deep Candidiasis
Figure 1. Four forms of invasive candidiasis
(www.doctorfungus.org) Zarqa Private UniversityBiology
4223 – The Fungi
Pathogenesis
Host Recognition
Adhesins
Enzymes
Hydrolases: Phosphoplipases, Lipases, Proteinases
Morphogenesis
Yeast form to Filamentous hyphae/pseudohyphae
Phenotypic Switching

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.

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 Figure 2. Morphogenic forms of Candida albicans
in host tissue. http://cbrrbc.nrccnrc.gc.ca/thomaslab/candida/caindex.html
(www.kent.ac.uk)
4223 – The Fungi
Subcutaneous Infections
Fungal Activity
 Fungi normally saprobic
 Introduced through wounds
 Adapt to the human animal by changes in
 morphology
 physiology

4223 – The Fungi
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
4223 – The Fungi
Mycotic Mycetoma
 Disease of barefoot tropical people
 Entry: wound on foot
 Attacks various tissues
 Stimulates formation of tumor
 Compact fungal colonies form within
tumor
4223 – The Fungi
 Skin ruptures and

some colonies
extrude

4223 – The Fungi
Systemic Mycoses
Introduction
 Caused by . . .
 Specialized pathogens
 Dimorphic
 One form outside the host
 Another form inside the host
 Opportunistic saprobes

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
4223 – The Fungi
Systemic Mycoses
 Histoplasma
capsulatum

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

4223 – The Fungi
Systemic Mycoses
 Infection, disease process, and clinical

symptoms similar to histoplasmosis
 Can be effectively treated with
fluconazole

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
4223 – The Fungi
Zygomycosis
 Species of Zygomycota
 Rhizopus, Mucor, Rhizomucor
 Rhinocerebral mycosis
 Spores enter through sinuses
 Grows rapidly outward to the eyes and
inward towards the brain

4223 – The Fungi
Aspergillosis
 Aspergillus sp.
 Bronchiopulmonary aspergillosis
 Mucus within the bronchi  severe

allergic reaction
 Aspergilloma
 Forms a mycelia ball in lung cavity

formed from earlier TB
4223 – The Fungi
 Surgical intervention often required

 Invasive aspergillosis
 Severely debilitated
 Immunosuppressed (AIDS)
 Almost always fatal until recently

4223 – The Fungi
AIDS and Mycoses
 Aspergillosis
 Candidiases (Candidiasis seen in 2/3 of
AIDS patients
 Cryptococcosis
 Zygomycosis
 Esophogeal candidiasis and
cryptococcosis are strong indicators of
AIDS
4223 – The Fungi
PRIMARY ANTI-FUNGAL
AGENTS
1. Polyene derivatives
 Amphotericin B
 Nystatin
2. Azoles
 Ketoconazole
 Fluconazole
 Itraconazole
 Voriconazole

4223 – The Fungi
4223 – The Fungi
Azoles
There are a few rare

serious side effects
from Itraconazole and
Fluconazole

4223 – The Fungi
5-fluorocytosine
(5-FC)
Interferes With RNA
Synthesis

4223 – The Fungi
MECHANISMS OF ACTION
 Polyenes  Ergosterol in cell

membrane
 Azoles
 Interfere with
ergosterol synthesis
 Forms a barrier to
 Griseofulvin fungal growth
 5 - FC  Inhibits RNA
synthesis
4223 – The Fungi

Medical Mycology

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Medical Mycology

Prof. Khaled H. Abu-Elteen

Zarqa Private UniversityBiology

 Mycosis- fungal infection

Zarqa Private UniversityBiology

 Spread by contact with fomites , cats and

Zarqa Private UniversityBiology

 Can spread throughout body

 Obligate Parasitic Fungi

Zarqa Private UniversityBiology

 Systemic infections: caused by true

Zarqa Private UniversityBiology

Zarqa Private UniversityBiology

Disseminated Histoplasma capsulatum, lung infection.

Zarqa Private UniversityBiology

Zarqa Private UniversityBiology

Ringworm skin infection: Tinea corporis

Candida albicans infection

 Infection occurs by implantation of spores or mycelial

IV. Superficial mycoses: Infections of hair shafts and

Zarqa Private UniversityBiology

 Microsporum (17 species)

 Trichophyton (24 species)

 50% of dermatophytes human specific

Zarqa Private UniversityBiology

 Cause common tinea (ringworm)

 Reservoir not in soil or animals

 Reservoir in carpets and upholstery

for up to two years

Zarqa Private UniversityBiology

Zarqa Private UniversityBiology

Zarqa Private UniversityBiology

 May move to humans or dogs

 Dies out after one or two person-

Zarqa Private UniversityBiology

skin to divide more frequently

 Some species body location specific

Zarqa Private UniversityBiology

 Candida albicans – candidiasis

 Excessive wetness  overgrowth on

Zarqa Private UniversityBiology

Zarqa Private UniversityBiology

Zarqa Private UniversityBiology

Zarqa Private UniversityBiology

Figure 1. skin equivalent before infection

Figure 2. Infection with pathogenic clinical isolate of C. albicans.

Figure 3. Infection with non-pathogenic C. albicans. This strain is not

Zarqa Private UniversityBiology

 Introduced through wounds

 Adapt to the human animal by changes in

Zarqa Private UniversityBiology

 Enters human by thorns or wood slivers

 Fungus grows  host cells respond by

 Entry: wound on foot

 Attacks various tissues

 Stimulates formation of tumor

 Compact fungal colonies form within