Medical Mycology

• It is the science
that deals with
the study of
pathogenic fungi
that produce
diseases.
 Medical Mycology
• Fungi were discovered earlier than bacteria
and viruses.
• In the past, most fungi caused skin infections
or cosmetic infections, where bacteria and
viruses cause serious fatal diseases, so there
was no interest of studying fungi.
• In 1980, when HIV infection was discovered,
increasing number of immunocompromizing
conditions, they found that fungi produce
fatal diseases; from that time, fungi return
to be in focus again.
 Structure

• Fungi are eukaryotic

organisms have true
nuclei with definite
nuclear membrane,
nucleolus, cytoplasmic
organelles.
 Structure
• Cell wall of fungi lacks:
– Peptidoglycan
– Glycerol & ribitol teichoic
acid
– Lipopolysaccharide
• Cell wall composed of:
– Chitin.
– Glucan (important for
new antifungal agent).
– Mannan.
 Fungal metabolism:

• All fungi are heterotrophic organism need to

parasite or saprophyte (on plant, animal or
human) to obtain organic source of carbon or
nitrogen.
• Most fungi are aerobic.
• Some are facultative anaerobes.
 Fungal metabolism:

• Optimum temperature of growth 25 – 30 ºC

(because most are saprophyte live in the
environment).
• Some are thermophilic, and can grow at
higher temperature.
• Fungi can tolerate a wide range of pH (2 – 9),
but generally they prefer acidic media.
Sexual
reproduction:
• Involve the union of
2 nuclei or 2 sex cells
or 2 sex organs.
Reproduction
Asexual
reproduction:
It is the main method of
reproduction.
 It includes:
– Fragmentation of hyphae & each
fragment grows into a new
individual fungus.
– Fission of cell into 2 daughter cells
(similar to binary fission in
bacteria).
– Budding of cells, each bud
produce
new individual (e.g. Candida).
– Formation of asexual spores.
 Fungal Spores

It is the method

of reproduction in
fungi unlike
bacteria.

Two types:
1-Sexual
2-Asexual
 Fungal Classification
a.According to morphology:
 Moulds (Filamentous fungi):
• Grow with formation of hyphae,
which may be septated or non-
septated.
 Moulds (Filamentous fungi):
– Vegetative mycelium:
• Some hyphae will
penetrate the media.
• Some hyphae present
at the surface of the
media.
– Aerial mycelium:
• Some hyphae may be
directed upward &
carry the different types
of spores that produced
by this fungus.
 Yeasts
– Unicellular fungi (rounded or
oval in shape).
– Reproduce by budding.
– The only example of pathogenic
yeasts is Cryptococcus
neoformans.
 Yeast-like
• Unicellular fungi (rounded
or oval in shape).
• Reproduce by budding.
• But during infection it
produces pseudohyphae.
• Example: Candida.
 Dimorphic fungi:
– Can grow as yeast during
infection in the body & on
incubating culture at 37 ºC.
– Can grow as moulds or
filaments when inoculated at
room temperature.
– Example: Histoplasma
capsulatum.
 Fungal Classification
B-According to nature of their sexual spores:
 Phycomycetes (Zygomycetes):
 Sexual spores are of 2 types:
– zygospores & oospores.
– Usually non-pathogenic.
 Source of
infection:
Endogenous:

•Normal flora and it is

the main source in
nosocomial infection
(because those people in
hospitals are
immunocompromized).
 Source of infection (cont.):
Exogenous:
•This is the main source of fungal infection
mainly from the environment.
•Few fungal infections are communicable
between human or between animals.
 Mode of transmission:
– Respiratory tract (air borne infection).

– GIT (food & water borne

infection).

– Blood stream
injection.

– Skin = contact.
– Most fungal diseases are not
communicable between human or
animals.
 Most fungi are opportunistic:
– Produce diseases in
immunocompromized
patients.
– Little is primary
pathogen (cause
disease in person with
intact immune
system).
 Steps of infection:

• I.Adherence:
– By adhesions, e.g. Candida, but filamentous fungi
have no adhesions.
– Fibrinonectin of epithelial cell is the receptors.
– Virulence usually associated with adherence.
 Steps of infection:
• ii. Invasion:
– Mechanical trauma to skin or mucosal
surface is an essential step in fungal
infection, because most of the infective
element in fungi is the spore and it is
non- invasive.
– Some fungi have invasive power like
Candida by the formation of hyphae
and pseudohyphae.
 Steps of infection:
• iii. Phagocytic interactions:
– Some fungi especially
dimorphic fungi show
resistance to phagocytic
killing.
– Some fungi are capsulated
and can resist phagocytosis
(Cryptococcus).
 Immunity to fungal
infections
Innate immunity:
– Non-specific works against all
microorganisms.
 Immunity to fungal
infections(cont.)
Acquired immunity:
The main immunity is cellular immunity
because fungi stay inside the host cell.

Antibodies have limited role in some

fungal diseases.
Human
mycosis
terminology
 A. Anatomical terminology
(According to the site
of infection): n

– Dermatomycosis: Fungal
infection of the skin.

– Pulmonary mycosis:
Fungal infection of the
lung.

– Cardiovascular mycosis:
Fungal infection of the
cardiovascular system.
B. Mycological terminology (According
to the etiology):
- Candidiasis (=
Candidiosis): Fungal
infection by Candida.
– Aspergillosis: Fungal
infection
by Aspergillus.
– Cryptococcosis: Fungal
infection by
Cryptococcus.
– Histoplasmosis: Fungal
infection by Histoplasma.
Types of human
mycosis
 Superficial mycosis
 Infection restricted to upper
most horny layer of skin,
hair and nails e.g. Pitryasis
versicolor.
 2 - Cutaneous mycosis:
•Ringworm fungi.
•Candidiasis of skin,
mucosal surfaces.
 3- Subcutaneous mycosis
(Implantation mycosis):
– Most of fungi are non
invasive.
– Occurs by implantation of
spores into wounds.
– e.g. Mycetoma (madura foot),
thorn pricks mycosis.
Fungal infections beneath the
skin.
 Caused by saprophytic fungi
that live in soil or on vegetation
 spread to lymph vessels.
 4- Systemic mycosis:
• Multi organs affected.
Mode of infection:
• Inhalation of spores of
saprophytic fungi.
• Spread of local
mycosis.

Examples:
• Cryptococcosis.
• Histoplasmosis.
• Candidiasis.
 5- Opportunistic mycosis:
• Fungal infection by:
– Fungal flora (Candida).
– Saprophytic fungi in the environment
(Aspergillus).
• This infection occur in:
– Immunocompromised host (Both innate
and acquired immunity).
– Opportunistic conditions like:
– Diabetic patients.
– Cancer patients.
– Corticosteroid & other
immunosuppressive therapy (e.g.
Cytotoxic drugs).
– Prolonged antibiotic therapy.
Opportunistic Infection by Candida albicans in
an AIDS Patient

Zarqa Private UniversityBiology 4223 –

The Fungi
Severe nail infection with Trichophyton rubrum in
a 37-year-old male AIDS patient.
Zarqa Private UniversityBiology 4223 –
The Fungi
Diagnosis of fungal infections
 1. Direct Microscopic Preparation:
• a) Unstained preparation
• Important and rapid method of diagnosis of fungal
infections.
• Scraping of lesion or bits of exudates (e.g. sputum, pus).
– Put on clean slide.
– Add drop of KOH (10 – 30%).
– Put cover slip.
– Gentle heating for 5 – 10 minutes (not direct heating).
– Examin by high power lens of the microscope.
– Find diagnostic fungal elements.
 1. Direct Microscopic Preparation:
• b) Stained
– Rapid and easy.
preparation:
– Cover slip preparation (KOH) may be stained with
IndiaLactophenol
ink cotton blue stain.
– India ink preparation is used for demonstration of
Cryptococcus neoformans. Cellotape
Flag
– Its positivity not more than Preparations.

30%.
 2. Culture for isolation of fungi:
• Sabouraud`s
dextrose agar (SDA):
– Composed of agar
+ dextrose +
peptone.
– Disadvantage:
Bacteria can grow
on it.
 2. Culture for isolation of fungi:
• SDA + Chloramphenicol (0.05%):
– Chloramphenicol is added to
inhibit bacterial growth.
 2. Culture for isolation of fungi:
• SDA + Chloramphenicol +
Cyclohexamide (0.5%):
– Cyclohexamide is added to inhibit
the growth of saprophytic fungal
contaminants.
 2. Culture for isolation of fungi:
• Blood agar:
– Some fungi as yeast, and yeast
like (Candida and Cryptococcus)
grow rapidly as bacteria after 4
weeks from incubation.
 Growth is identified by:
• Macroscopic
characters: e.g. colour
from both sides (recto
– verso examination),
shape, size and texture
of the colony.
• Microscopic stained
preparation.
• Biochemical reaction:
Sugar fermentation and
assimilation (especially
in yeast).
 4. Histopathology:
Yeast cells:
•They may be
intracellular small yeast:
e.g. Histoplasma
capsulatum.
– They may have a
large distinguishing
capsule: e.g.
Cryptococcus.
 4. Histopathology:
• Spherules:
– Intact spherules
are large sac-like
structure filled
with
sporangiospores.
Left: A patient showing the
disseminated stage of disease
(coccidioidomycosis).
Top right: spherules.
Bottom right: chains of
arthrospores interspersed with
empty cellular compartments.
 4. Histopathology:
• Hyphae:
– They may be brown in colour or non-coloured.
– They may be septated or non-septated.
 4. Histopathology:

• Granules:
– They are tightly packed
masses of hyphae or
filaments, which are
surrounded by tough outer
rind.
 4. Histopathology:
 Combination of
yeast cells and
hyphae: As in
Candida.
 5. Woods light:
• Helps in clinical
diagnosis.
• Long wave ultraviolet
rays (black rays) which
when come in contact
with mycotic areas of
skin and hair produce
fluorescent colours.
• Disadvantage: it occurs
in some mycotic
infections only.
 6. Indirect method of diagnosis:
• Detection of circulating antibodies
(Serological diagnosis):
• It has limited role.
• Used in diagnosis and follow up of Cryptococcus and
Candida with limits.
 Tests used for detecting
fungal
– Precipitationantibodies:
ELISA AGGLUTINATION
precipitation Electrophoresis
reaction.
– Agglutination.
– Electrophoretic tests.
– Complement fixation.
– Indirect fluorescent antibody.
– ELISA.
 Fungal skin tests:
• It has no value in
diagnosis.
• It does not differentiate
between active and past
infection.
• Mainly used for
epidemiological study.
• It is observed by
formation of induration
and swelling due to
reaction between injected
antigen and T cells.
• e.g. Histoplasmin,
Candidin, Tricophytin
tests.
 Antifungal therapy
• Topical antifungals:
– Polyenes e.g. nystatin,
fungizone
– Azoles (e.g. miconazole,
Ketoconazole, econazole,
clotrimazole).
– Miscellaneous e.g tolanftate,
allylamine, iodine.
 Systemic antifungals:

Polyenes (e.g Amphotericin-B).

5-flucytosine.
Azoles (e.g itraconazole,
fluconazole).
Terbinafine.
Griseofulvin
Iodine.
New antifungal
• Echinocandins e.g caspofungin
 Mechanism of action of
antifungal

Nucleic acid
Cell synthesis
Cell wall
membrane 5-Flucytosin
Cuspofungin
Griseofulvin
Polyenes
Azoles
 How to select proper
antifungal drug?
–We can select proper
antifungal drug via
susceptibility testing
method e.g
– Broth dilution method
– Agar diffusion
method
I. Superficial
fungal
infection
 A. Ring worm fungi
(Tinea =dermatophytosis)
,
Dermatophytosis
• Fungal infection by
dermatophytes of
keratinous
structures (skin, hair
n
ails).
 A. Ring worm fungi

Com mon clinical

types:
1. Tinea Corporus:
• Dermatophyte
infection of the
glabrous skin
(trunk, back,
dorsum of the
hand).
 A. Ring worm fungi
Common clinical types:
2. Tinea Capitis:

• Fungal infection of the

skin of the scalp and hair.
• This takes 3 forms of hair
involvement:
• a) Endothrix:
– There is abundant fungus growth
inside the hair shaft.
• b) Ectothrix:
– The spores surround the hair shaft from outside
lead to weakness and falling of the hair.
• c) Favic type:
– Some fungal mycelia are present inside the shaft
with air space.
 A. Ring worm fungi
Common clinical types:
3. Tinea Barbae:

• Fungal
infection of
the beard and
moustache
skin area in
male.
 A. Ring worm fungi Common clinical
types:
4. Tinea Pedis (Athlete's foot):

–Ring worm of the foot.

–It is infection of the feet or toes
with dermatophyte fungus
–include soles, nails and inter-digital
peeling.
 A. Ring worm fungi
Common clinical types:
5. Tinea Manum:
– Fungal infection
of the palm of the
hand and inter-
digital areas.
A. Ring worm fungi
Common clinical
types:
7. Tinea cruris
– Fungal
infection of the
crural area and
perineum.
 A. Ring worm fungi
Common
clinical types:
7. Tinea
Unguim:

– Fungal
infection of
the nail of
the hand and
toes
 Epidemiology
According to the source of
infection
 1- Anthroprophilic:
Epidermophyton
–From human to
human.
–e.g.
Epidermophyton
flocosum.
 2- Zoophilic:
– From animal Microsporum canis

to human.
– e.g.
Microsporum
canis.
 3- Geophilic:
Microsporum
– Spores found gypseum

in soil.
– e.g.
Microsporum
gypseum.