MEDICALLY IMPORTANT

FUNGI

DR. BREIDA BOYLE

 INTRODUCTION
Fungi are a diverse group of sacrophytic and
parasitic eukaryotic organisms
Kingdom: Mycota
Of 100,000 fungal species only 100 have
pathogenic potential for humans, only a few
account for clinically important infections
Mycoses : Human Fungal Diseases
Fungal spores may be important as human
allergenic agents
 INTRODUCTION
MYCOSES
CUTANEOUS: limited to the dermis
SUBCUTANEOUS : when infection
penetrates significantly beneath the skin
SYSTEMIC : when the infection is deep
within the body or disseminated to internal
organs
 PATHOGENIC FUNGI

TRUE OPPORTUNISTIC
PATHOGENS PATHOGENS
 TRUE PATHOGENS
Cutaneous infective agents
Epidermophyton species
Microsporum species
Trichophyton species
Subcutaneous infective agents
Actinomadura madurae
Cladosporium
Madurella grisea
Phialophora
Sporothrix schenckii

Systemic infective agents

Blastomyces dermatitidis
Coccidioides immitis
Histoplasma capsulatum
Paracoccidioides brasiliensis
OPPORTUNISTIC
PATHOGENS

Absidia corymbifera
Aspergillus fumigatus
Candida albicans
Crytococcus neoformans
Pneumocystis carinii
Rhizomucor pusillus
Rhizopus oryzae (R.arrhizus)
CLASSIFICATION OF FUNGI
Depends on :
Characteristic Structures
Habitats
Modes of Growth
Modes of Reproduction
 Cell Wall and Membrane
Composed mainly of chitin rather than
peptidoglycan (bacteria)-so unaffected by
antibiotics
Chitin: consists of a polymer of N-
acetylglucosamine
Fungal Membrane contains ergosterol rather than
cholesterol found in mammalian cells, use in
antifungal agents such as amphotericin which
binds to ergosterolpores that disrupts membrane
function cell death
 Cell Membrane
The imidazole antifungal drugs
( clotrimazole, ketoconazole, miconazole)
and the triazole antifungal agents
(fluconazole , itraconazole) interact with the
C-14 -demethylase to block demethylation
of lansterol to ergosterol, vital component
of cell membrane and disruption of it`s
synthesis results in death
 HABITAT
All fungi are heterotrophs ( their require some
form of organic carbon for growth)
They depend on transport of soluble nutrients
across their cell membrane
To do this they secrete degradative enzymes (
proteases etc) into their immediate environment,
therefore they live on dead organic material
So Natural Habitat : is soil or water containing
decaying organic matter
 MODES OF FUNGAL
GROWTH

UNICELLULAR
FILAMENTOUS
YEASTS
MOLDS

However there are some dimorphic fungi ( they switch between these
Two forms depending on their environment)
Filamentous (mold-like) Fungi
Thallus (vegetitive body)
mass of threads with
many branches resembling
cotton ball
Mass: mycelium
Threads: hyphae, tubular
cells that in some fungi
are divided into segments
septate whereas in other
fungi the hyphae are
uninterrupted by
crosswalls-nonseptate
Grow by branching and tip
elongation
 YEAST like FUNGI
These fungi exist as
populations of single ,
unconnected , spheroid
cells, not unlike many
bacteria, although they are
sometimes 10 times larger
than a typical bacterial cell
Yeasts reproduce by
budding
Some fungal species
particularly those that
cause systemic infection
exist as dimorphic fungi
REPRODUCTION
 SPORULATION
The principle way in which fungi reproduce and
spread within the environment
Fungal spores are metabolically dormant,
protected cells, released by the mycelium in
enormous numbers
Borne by the air or water to new sites , where they
germinate and establish new colonies
Spores can be generate sexually or asexually
 ASEXUAL SPORULATION
(MITOSIS)

Colour of a particular fungus seen on bread, culture plate is due to the

Conidia, easly airborne and disseminated
 SEXUAL SPORULATION
meiosis

Relatively rare compared to asexual sporulation, and spore shape often

Used as a method of identification
 CUTANEOUS MYCOSES
-DERMATOPHYTOSES
EPIDEMIOLOGY
Three genera-Trichophyton, Epidermophyton,
Microsporum
Anthropophilic-reside on the human skin
Zoophilic-reside on the skin of domestic and farm
animals
Geophilic-reside in the soil
Transmission from humans or animals is by
infected skin scales
 PATHOLOGY
Dermatophytes use keratin as a source of
nutrition
Therefore they infect skin, hair, nails
All 3 organisms infect attack skin,
Microsporum does not infect nails and
Epidermophyton does not infect hair, they
not invade underlying non-keratinized
tissues
 CLINICAL SIGNIFICANCE
DERMATOPHYTOSES
Characterized by itching,scaling skin
patches that can become inflamed and
weeping
Infection in different sites may be due to
different organisms but is given one name
 Tinea pedis(Athlete`s foot)
Common organisms are
Trichophyton rubrum ,
Trichophyton
mentagrophytes and
Epidermophyton
floccosum.
Initially between the toes
spreads to nails, yellow
and brittle
Secondary bacterial
infection
Id Reaction
Tinea corporis( Ringworm)
Epidermophyton
floccosum, Trichophyton,
Microsporum
Advancing annular rings
with scaly center
Periphery of ring area of
active fungal growth,
usually inflammed and
vesiculated
Non-Hairy areas of trunks
mostly
Tinea capitis( scalp ringworm)
Trichophyton and
Microsporum
Depends on area
Small scaling patches
to involvement of
entire hair with
hairloss
Microsporum infects
hair shafts , Wood`s
lamp
 TINEA CRURIS/UNGUIUM
Epidermophyton ,
Trichophyton rubrum,
simliar to ringworm but
thighs and genitalia
Trichophyton rubrum,
nails thickened
discoloured and brittle
Treatment for months until
all of the infected nail
grows out and is trimmed
off
 Treatment
Samples to be sent for fungal staining and culture
Infected skin may be treated with topical
application of antifungal agents miconazole and
clotrimazole
Refractory lesions oral griseofulvin and
itraconazole, terbinafine
Infections of hair and nails usually require
systemic ( oral) therapy
 SUBCUTANEOUS
MYCOSES( dermis, subc
tissues and Bone)
Causative organisms reside in the soil and in
decaying or live vegetation
Almost always acquired through traumatic
lacerations or puncture wounds
Common among those who work with soil and
vegetation and have little protective clothing
Not usually transmitted humans to humans
Usually confined to tropics and subtropics with
exception of Sporotrichosis in USA
 Sporotrichosis
Sporothrix schenckii-dimorphic fungus
Granauloma ulcer at a puncture skin usually a
thorn prick and may produce secondary lesions
along draining lymphatics
In most disease is self-limiting may exist in
chronic form
Treatment oral itraconazole
Chromomycosis : Phialophora or Cladosporium
 Mycetoma
Madurella grisea,
Actinomadura madura
Localized abscess usually
on the feet, that discharge
pus serum and blood
Has coloured grains(
compact hyphae) black,
white, red or yellow
depending on organism
 Eastern US

Males
Diagram of Systemis mycoses(dimorphic, yeast in infective tissue)
 Clinical significance
Simliar to Tb in that asymtomatic primary
infection is seen whereas chronic
pulmonary or disseminated infection rare
In the immunocompetent usually mild and
self limiting
In the immunocompromised the same
infections can be life threatening
 Coccidiodomycosis
Coccidioides immitis
Most in arid areas of south-western US
In the soil forms arthrospores
Spores airborne , germinate in the lungs and
produce sphercules filled with many
endospores- new spherule
In disseminated cases lesions in the bone or
CNS -meningitis
 Histoplasmosis
Histoplasma capsulatum
In the soil conidia,
germinate lungs into
yeast-like cells
Becomes engulfed by
macrophages and XX
Benign self-limiting or
chronic, progressive , fatal
Disseminated disease only
fungus intracellular RES
parasitism
Area Ohio and Mississippi
River area
AIDS patients at particular risk
DX: Culture or
Treatment : Amphotericin Exoantigen
or Itraconazole (immunodiffusion assay)
OPPORTUNISTIC
PATHOGENS

Absidia corymbifera
Aspergillus fumigatus
Candida albicans
Crytococcus neoformans
Pneumocystis carinii
Rhizomucor pusillus
Rhizopus oryzae (R.arrhizus)
OPPORTUNISTIC MYCOSES
Those that affect the immunocompromised
but are rare in normal individual
Organ transplantation, post chemotherapy
for cancer, immunodeficient due to Aids and
congenital immunodeficiency states
Candida species most commonly occurring
fungal pathogen in the ICU setting
 CANDIDIASIS(candidiosis)
Candida albicans and other candida species which
are normal flora in the mouth, skin , vagina and
intestines
C.albicans is dimorphic
May occur as a results of overgrowth as
suppression of bacteria by antibiotics
Manifestations depend on the site e.g. oral
candidiasis and vaginal candidiasis and
disseminated candidiasis in cancer patients, post
GI surgery and AB`s, systemic corticosteroids
 CRYTOCOCCOSIS
Crytococcus neoformans, found worldwide
Especially found in soil containing bird(esp.
pigeons) droppings
Characteristic thick capsule that surrounds
budding yeast cell seen Indian Ink
Most common form is mild subclinical lung
infection
In the immunocompromised often disseminates to
the brain , meningitis often fatal
However half those with crytococcal meningitis
have no obvious immune deficiency
 ASPERGILLOSIS
Several species of genus Aspergillus, mostly
Aspergillus fumigatus
Worldwide distribution, ubiquitous
Filamentous molds, produce large numbers of
conidiospores
Reside in soil, decomposing organic matter and
dust, associated outbreks with construction work
Disease presentation depends on immunologic
status of patient
 ASPERGILLOSIS
Acute Aspergillus infections
Most severe and often fatal form of
aspergillosis is acute invasive infection of
the lungdissemination to brain etc
Less severe form gives rise to a fungus ball(
aspergilloma) , a mass of hyphal tissue that
forms in lung cavities derived from prior
disease
 Allergic Aspergillosis
Relatively rare, can arise from inhalation of
spores, without sussequent extensive spore
germination hyphal invasion
The allergic reaction results in bronchial
constriction
Diagnosis by immunoelectrophoresis
 MUCORMYCOSIS
Most often caused by Rhizopus oryzae and less
often by other members of the Mucorales such as
Absidia corymbifera, Rhizopus pus
Ubiquitous in nature, spores found in great
abdunance on rotting fruit and old bread
Usually restricted to those with underlying
conditions such as burns, leukaemia or diabetus
mellitus
The most common form of the disease can be fatal
within a week-Rhino cerebral Mucormycosis
 PNEUMOCYSTIS CARINII
PNEUMONIA
Caused by a unicellular eukaryote, Pneumocystis
carinii
Before the use of immunosuppressive agents and
the onset of the AIDS epidemic , PCP was a rare
disease
It is one of the most common opportunisitic
diseasesof individuals treated with HIV-1 and
usually fatal if untreated
It does not contain ergosterol and has not been
cultured
 PCP
Various cellular forms encysted group of dormant
cells and vegetitive form trophozoite
Ubiquitous
Activation of preexisting dormant cells in the
lungs in immunodeficient persons
The encysted forms induce an inflammination of
the alveoli-exudate which blocks gas exchange
Diagnosis by microscopic examination , by silver
stain or fluorescence of bronchial washings or
biopsy
 LABORATORY
IDENTIFICATION
Standard media Sabouraud`s agar, potato
dextrose agar, low ph 5.0 , inhibits bacterial
growth but allows fungal colonies to form
Cultures can be started from spores or hyphae
fragments
Specimens: blood, pus, CSF, sputum, tissue
biopsies, skin scrapings , nail clippings
Identification by the morphology of conidia
structures and carbonhydrate assimiliation tests
 LABORATORY DIAGNOSIS
OF FUNGAL INFECTION
Specimens
Depends on site of infection
Systemic: -Blood culture( really only useful for
yeast-low sensitivity) or
- antigen testing e.g.crytococcal
and histoplamsosis antigen
Pneumonia: Bronchoscopy washings or
brushings for staining and fungal culture or
bronchial biopsy
 LABORATORY DIAGNOSIS
OF FUNGAL INFECTIONS
Meningitis: Cerebrospinal fluid for
methylene blue staining and indian ink and
crytococcal antigen and fungal culture
If Skin infection require skin scrapings
If nail infection require nail clippings
Galactomannan antigen testing for
aspergillus infection
 LABORATORY DIAGNOSIS
FUNGAL INFECTIONS
Types of tests carried out
Fungal Staining methylene blue staining or wet
prep using KOH to dissolve tissue material
Fungal culture on media that encourages fungal
growth e.g. PDA
Antigen Testing i.e. to test for antigen present in
the wall of fungus e.g crytococcal antigen,
galactomannan used in serum and CSF samples
PCR not used on a routine basis on samples
MANAGEMENT OF FUNGAL
INFECTIONS
Some such as superfical skin infections require
topical therapy only with cream e.g.nystatin cream
Some require local therpy e.g. pessaries for
vaginal candidasis
Some require oral therapy for skin and nail
infections up to 1 year e.g. terbinafine
In the immunocompromised systemic therapy
required e.g. , voriconazole,fluconazole i./v or
amphotericin
MANAGEMENT OF FUNGAL
INFECTIONS
Important to diagnose fungal infections
early in the immunocompromised as there is
a high mortality associated with infection
Empirical therapy often started in advance
of laboratory diagnosis in these patients