Lecture 4-Medical Mycology-.ppt

Zarqa Private UniversityBiology
4223 – The Fungi
Medical Mycology
Prof. Khaled H. Abu-Elteen

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 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

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 of the nails.

4223 – The Fungi
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 thin-walled dimorphic fungus
Morphogenesis
Unicellular yeast (harmeless)
Filamentous (pathogenic)
Principal Cell Wall Polymers
Gluccan
Mannan
Strict aerobe, favors moist surfaces
Commensally found in gut, genitals, and lungs
Body Temp 37º C, neutral pH
Figure 1. Yeast in Oral Scraping
A sample of an oral scraping contains yeast cells and
pseudohyphae
(www.doctorfungus.org)
Rapid Multiplication & Spread

4223 – The Fungi
Diseases by C. albicans
Thrush
Esophagitis
Cutaneous Candidiasis
Genital Yeast Infections
Deep Candidiasis

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

4223 – The Fungi
Genital Yeast Candidiasis
Symptoms
Risk Factors
- disruption of normal
microbiota
Treatment
- direct genital administration
- tablets, suppositories, creams
Figure 1. Vaginal Yeast Culture
Figure 2. Plasma cell balanitis. A
band-like infiltrate of plasma cells is in
the dermis of the male penis.

4223 – The Fungi
Deep Candidiasis
Figure 1. Four forms of invasive candidiasis
(www.doctorfungus.org)

4223 – The Fungi
Pathogenesis
Host Recognition
Adhesins
Enzymes
Hydrolases: Phosphoplipases, Lipases, Proteinases
Morphogenesis
Yeast form to Filamentous hyphae/pseudohyphae
Phenotypic Switching

4223 – The Fungi
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.
Virulence assay of different C. albicans strains using the skin equivalent (AST 2000)
(Fraunhofer, 2002)

4223 – The Fungi
MORPHOGENESIS
Figure 2. Morphogenic forms of Candida albicans
http://cbr-rbc.nrc-cnrc.gc.ca/thomaslab/candida/caindex.html
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)

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

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