FINALS TOPIC 1 : MEDICAL MYCOLOGY 2017 || DR.

KATH CALIGAGAN
PAGE 1
MEDICAL MYCOLOGY  Some fungi are human pathogens (300 out of 200,000
FUNDAMENTALS OF MYCOLOGY species)
 reproduce both sexually & asexually via production
IMPORTANCE of spores.
1. Responsible for the majority of plant, animal and human 1. ASEXUAL reproduction: produces two major types
diseases of asexual spores:
2. Agents of biodegradation and biodeterioration
3. Used in industrial fermentation processes
a. SPORANGIOSPORES
4. Used in the commercial production of many biochemicals - ENDOGENOUS - formed and
5. Provide us with a direct source of food contained within a
6. Used in bioremediation such as reducing the concentrations SPORANGIUM.
and toxicities of waste materials - characteristic of fungi belonging to
7. Highly beneficial in agriculture, horticulture and forestry the CHYTRIDIOMYCOTA,
8. Used in the biological control of insect and nematode pests, OOMYCOTA and
weeds and pathogenic microorganisms HYPHOCHYTRIDIOMYCOTA.
- Two main types: ZOOSPORES
CHARACTERISTICS (motile) and APLANOSPORES
(non-motile)
 Eukaryotic b. CONIDIA
 Cell wall composed of chitin - EXOGENOUS - often formed at
 CHITIN - major structural polymer in fungal cell the tip of supporting hyphae called
walls. It is a polysaccharide composed of long a CONIDIOPHORES
chain of n-acetyleglucasamine. - characteristic of MITOSPORIC
 B-GLUCAN - site of action of some antifungal FUNGI and fungi belonging to the
drugs ASCOMYCOTA and
 Cell membrane consists of ergosterol BASIDIOMYCOTA.
 ERGOSTEROL - site of action of antifungal - Two main types: THALLIC
drugs, amphtericin B & azole group (develop by septation or
fragmentation of a hypha) and
BLASTIC (develop by budding or
swelling).

2. SEXUAL reproduction:
a. ZYGOSPORES are formed by the
fusion of cells and nuclei from opposite
mating strains

ASEXUAL SPORES
 exhibit a wide variability in coloration, texture, size,
shape, number of cells, cellular arrangement, and the
manner in which they are borne on the mycelium
 All are achlorophyllous. They lack chlorophyll  the morphology of the fungus depends upon the
pigments and are incapable of photosynthesis arrangement of the spores and how they are produced
 Capable of chemoheterotrophic, aerobic, and and these features are used for identification of
facultative anaerobic respiration. Some are also genera and species
capable of fermentation
 Are saprophytes, especially the mold form. They
derive nutrients and energy from dead and decaying
matter
 Nutrients are acquired via simple absorption
(diffusion)
 Inhabit the environment, both terrestrial & aquatic
 Exception: Candida albicans is part of normal
human flora.

 May be free-living or may form intimate

relationships with other organisms
 Most parasitic fungi are plant pathogens
 FINALS TOPIC 1 : MEDICAL MYCOLOGY 2017 || DR. KATH CALIGAGAN
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2. CHLAMYDOCONIDIA
- develop in an INTERCALARY (central)
position
- thick wall - serves as storage of food
reserves

BLASTIC CONIDIA

THALLIC CONIDIA - Develop by BUDDING or SWELLING of a hypha

which may develop as single spores or in
- Develop by SEPTATION and succession to form a chain of conidia
FRAGMENTATION of a hypha - Includes:
- Includes:
1. ARTHOCONIDIA 1. BLASTOCONIDIA
- released by the fragmentation or lysis of - spore may remain attached and bud further forming
hypha blastospores- giving rise to a branched chain of
- develop at the tip of a hypha spores
- each fragment is rounded off and liberated
in succession
- all layers of the hypha become converted
into conidia and are involved in spore
formation

2. PHIALOCONIDIA
- each spore is pushed up from the tip of the
conidiophore, which is now called a PHIALIDE
- the spore wall is new and distinct from both wall
layers of the phialide
- the first spore has a cap, which represents the tip of
the phialide wall through which the spore emerged;
all other spores in the chain are smoothly rounded
 FINALS TOPIC 1 : MEDICAL MYCOLOGY 2017 || DR. KATH CALIGAGAN
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- HYPHAE basic morphological elements of
3. ANELLOCONIDIA filamentous fungi consists of one or more cells,
ANNELLATIONS/ANNELIDES (ring-like scars) are surrounded by a tubular cell wall. Some fungi
observed around the elongating portion - a conidiogenous have septated hyphae, meaning the hyphae are
cell that gives rise to successive conidia in a basipetal divided into cells by internal cross-walls called
manner. The apex of an annellide becomes longer and SEPTUM. Some have aseptate hyphae
narrower as each subsequent conidium is formed and (COENOCYTIC), meaning their hypahe are not
released. An apical ring composed of outer cell wall partitioned by septa. They grow at their tips. The
material remains as each conidium is released SPITZENKORPER or APICAL VESICULAR
CLUSTER (AVC) is an intracellular organelle
associated with tip growth.

Two types (Mycelium)

4. POROCONIDIA
pore emerges through a distinct 'pore' in the hyphal wall.
the outer spore wall is often thickened and pigmented. A
scar is usually obvious at the point of detachment from
the hypha
1. STOLON or AERIAL or REPRODUCTIVE
- horizontal filaments or horizontally expanding
septated hypahe that connects sporangiosphores
together.
- responsible for reproduction
2. RHIZOIDS or VEGETATIVE
- root-like, small branching hyphae that grow
downwards from the stolons that anchor the fungus
to the substrate, where they release digestive
enzymes and absorb digested organic material
- responsible for gaining nutrients

5. ALEURIOCONIDIA
develop as single, terminal spores. The spore possesses a
wide, truncate scar

CHARACTERISTICS OF FUNGI

TYPES
1. Filamentous or molds
2. Yeast
3. Yeast-like
4. Thermal dimorphic

MORPHOLOGY

1. MOLDS or FILAMENTOUS or HYPHAE

- multicellular fungi which reproduce asexually and/or

sexually by production of multicellular filamentous
colonies consisting of branching cylindric tubules called
HYPHAE, which intertwine to produce a mass of
filaments called MYCELIUM (molds) that accumulates
during active growth
 FINALS TOPIC 1 : MEDICAL MYCOLOGY 2017 || DR. KATH CALIGAGAN
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2. YEAST

- most common fungal isolate from patients

- are normal components of gastrointestinal and
genitourinary tracts
- only pathogenic yeast in medical mycology is
Cryptococcus neoformans
o a rapidly growing unicellular, eukaryotic,
generally round to oval(5-10µm) capable of
producing polysaccharide capsules which
often surround the cell

- reproduce principally by blastoconidia or budding

Trychophyton tonsurans
forming buds known as blastospores
- some may produce ascospores
- produce true hyphae
- colonies resemble bacterial colonies in appearance
and in consistency (not so helpful in identification
by morphology)
- biochemical tests are usually necessary for
definitive diagnosis
o Growth at 37°, germ tube test, carbohydrate
assimilation, fermentation, urease test, and
phenol oxidase test may be employed

Microsporum gypseum
 FINALS TOPIC 1 : MEDICAL MYCOLOGY 2017 || DR. KATH CALIGAGAN
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3. YEAST-LIKE

- occurs in the form of budding yeast-like cells and

as chains of elongated unbranched filamentous
cells which present the appearance of broad septate
pseudohyphae, which intertwine to form a
pseudomycelium
- grouped together in the genus Candida
o causes Candidiasis, commonly called yeast
infection or thrush
o grow at 37°, ferment glucose and may
ferment other carbohydrates, and form
pseudo- or true hyphae
o harbored by the gastrointestinal tract
o creamy colonies, as other yeasts

4. THERMAL DIMORPHIC
- these are fungi which exhibit a filamentous KINGDOM
mycelial morphology (saprophytic phase) when
grown at room temperature 25-30oC, but have a 1. CHYTRIDIOMYCOTA
typical yeast morphology (parasitic phase) inside - most ancient group of fungi
the body and when grown at 35-37oC in the - smallest and simplest fungi
laboratory - asexual reproduction results to formation of zoospore
Examples: (motile sporongiospore) with a single whiplash
Histoplasma capsulatum Paracoccidioides brasiliensis flagellum.
Sporothrix schenckii Coccidioides immitis
Blastomyces dermatitidis Penicillium marneffei 2. ASCOMYCOTA/ASCOMYCETES
- largest, comprising 60% of known fungi and 85% of
human pathogen
 FINALS TOPIC 1 : MEDICAL MYCOLOGY 2017 || DR. KATH CALIGAGAN
- sexual reproduction involves a sac or ascus in which
karyogamy and meiosis occur, producing ascospores
- asexual reproduction is via conidia
- have septated hyphae
- Eg) Ajellomyces (Blastomyces, Histoplasma),
Arthroderma
(Microsporum,
Trichophyton),
Coccidioides, and
Yeast
(Saccharomyces
and Candida)
3. ASCOMYCOTA/ASCOMYCETES
- sexual reproduction results in a zygospores
- asexual reproduction results to formation of
zoospore/zoosporangiospore (motile
sporangiospore)
- have pauciseptate hyphae (means there are a few
septations or can be a few septations but for the
most part the hyphae do not have septations within
them. Vegetative hyphae are sparsely septate)
- may have root-like structures called rhizoids that
anchor them to the substrate surface
- very rapid growth (hallmark)
- Eg) Rhizopus, Absidia, Mucor, Pilobolus
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EPIDEMIOLOGY
 Fungi and their spores are almost everywhere in the
environment
 Epidemics result from mass exposure to
environmental source of fungi
 Are generally not reportable
 Most people will experience a mycosis at some time
 Typically acquired via inhalation, trauma, or
ingestion
o PORTAL OF ENTRY: skin, hair , nails, RT,
GIT, GUT
 Infrequently spread from person to person
 Most mycoses are not contagious
o Dermatophytes are the major exception
HOST DEFENSES
 In general, humans have a high level of innate
immunity to fungi
 This resistance is due to:
o Fatty acid content of the skin
o pH of the skin, mucosal surfaces and body fluids
o Epithelial turnover
o Normal flora
o Transferrin
o Cilia of respiratory tract
 Most of the infections they cause are mild and self-
limiting

4. BASIDIOMYCOTA/BASIDIOMYCETES DIAGNOSIS
- sexual reproduction results in four progeny  Patient’s history
basiodiophores supported by a club-shaped  Definitive diagnosis often requires morphological
basidium analysis of the fungus involved through microscopy
- asexual reproduction is conidia  Sabouraud dextrose agar used to culture fungi
- Hyphae have complex septa  Various techniques to detect fungal cells in patient
- Eg) Mushrooms, Filobasidiella neoformans specimens
(Cryptococcus neoformans) o Wet Mount using 10 % KOH (may add
Calcofluor white as a fluorescent brightener)
MEDICAL MYCOLOGY o Skin test (dermal hypersensitivity)
o Serology
- Is the study of mycoses of man and their etiologic o Fluorescent antibody
agents o Biopsy and histopathology
- Of the 100,000-200,000 of species of fungi that are o DNA probes
known, less than 300 are pathogenic to man
- MYCOSES are the diseases caused by fungi
o among the most difficult diseases to diagnose
and treat
 signs of mycoses are often missed or
misinterpreted
 fungi are often resistant to antifungal
agents
- Pathogenecity of fungi: thermotolerance, ability to
survive in tissue environment, ability to withstand
host defenses
- Establishment of infection with a mycotic agent
depends on: inoculum size, resistance of the host
- Severity of disease depends more on the host
immune system than on the virulence of the fungus
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TREATMENT
Primary ANTI-FUNGAL AGENTS 3. ALLYLAMINES
Naftifine , Terbinafine
MOA: binds to and inhibits squalene epoxidase which
blocks ergosterol synthesis

1. POLEYENE DERIVATIVES
Amphotericin B
is the gold standard of antifungals
MOA: binds to ergosterol moiety in the plasma
membrane causing derangement of the membrane
integrity and leakage of cytoplasmic contents (has a
greater avidity for ergosterol than for the cholesterol
in the human cell wall)
DISADVANTAGES:
- intravenous administration, thrombophlebitis,
nephrotoxic, fever, chills, anemia, long term
administration
- administered systemically
Nystatin
MOA: binds to ergosterol and disrupts plasma
membrane
- highly insoluble and toxic and therefore used
topically only
2. AZOLES
MOA: all effects are due to the binding to cytochrome
P-450 which interfere with ergosterol synthesis (block
ergosterol synthesis at one or more sites with the
accumulation of 14 -methyl sterol which replaces
ergosterol in the plasma membrane causing selective
leakage and increased osmotic sensitivity. They also
disrupt chitin synthesis ; broad-spectrum of activity
4. PYRIMIDINE ANALOGS
5-fluorocytosine (5-FC)
MOA: deaminated to fluracil where it is either:
- incorporated into RNA in place of uracil where it
inhibits protein synthesis or;
- metabolized to 5-fluorodeoxy-uridylic acid
where it inhibits thymidylate synthetase, thus
blocking DNA synthesis
5. GRISEOFULVIN
MOA: causes disruption of the mitotic spindle by
interacting with polymerized microtubules through
binding to microtubule protein
it accumulates in the stratum corneum and prevent hyphal
penetration through these layers (forms a barrier to fungal
growth)
a slow acting drug used for skin and nail infections
administered systemically for dermatophytic infections
6. ECHINOCANDINS (Caspofungin)
Misc.:
7. HALOPROGIN
a halogenated phenolic ether ; administered topically for
dermatophytic infections
8. CICLOPIROX OLAMINE
a topical drug for the treatment of dermatophytic
infections and Candida albicans
9. TOLNAFTATE
a thiocarbonate used to treat dermatophytic infections
10. POTASSIUM IODIDE
given orally for sporotrichosis

Butoconazole (Suppository, Topical)

Clotrimazole (Topical)
Econazole (Topical)
Fluconazole (Oral, Topical)
Itraconazole (Oral)
Ketoconazole (Oral, Topical)
Miconazole (IV, Intrathecal, Topical)
Oxiconazole (Topical)
Sulconazole (Topical)
Terconazole (Suppository, Topical)
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ANTI-FUNGAL VACCINES
Difficult to develop since fungal metabolism is similar to
our own. Therefore it is difficult to develop vaccines or
chemotherapeutic agents that will destroy the invading
fungus without harming the patient

Vaccines against some fungi

- Coccidioides
- Candida
- Blastomycosis

MANIFESTATION OF FUNGAL DISEASE

1. INFECTION
- Most common
- Caused by presence of true or opportunistic
pathogens PATHOGENIC INFECTION
- Categories:
o PATHOGENIC INFECTION A. SUPERFICIAL MYCOSES
 Superficial
 Cutaneous - Superficial cosmetic fungal infections limited to the
 Subcutaneous outermost layers of the skin, nail and hair
 Systemic - No living tissue is invaded, no pathological changes
o OPPORTUNISTIC INFECTION are elicited, and no cellular response from the host
- Most common fungal infections (together with the
2. HYPERSENSITIVITY dermatophytes)
- Most often result from the inhalation of fungal
spores/allergens
- Cause Type I hypersensitivity reactions that can
result in asthma, eczema, and hay fever
- Type III hypersensitivity reactions occur much less
frequently
- Examples:
o FARMER’S LUNG: moldy hay
o MALT WORKER’S DISEASE: moldy barley
o CHEESE WASHER’S LUNG: moldy cheese
o WOOD TRIMMER’S DISEASE: moldy wood

3. TOXICOSES
TYPES:
B. CUTANEOUS MYCOSES
- Mycotoxicoses
o acquired through ingestion often from grains or
- Superficial fungal infections that extend deeper into
vegetables containing mycotoxin (poisonous
the epidermis, as well as invasive hair and nail
toxins produced by fungi during normal
diseases
metabolic activities )
- Restricted to the keratinized layers of the skin, hair
o AFLATOXINS are the most well-known
and nails
mycotoxin
- No living tissue is invaded but unlike the superficial
o Fatal to many vertebrates
mycoses, various cellular immune responses may be
o Carcinogenic at low levels when consumed
evoked, causing pathologic changes in the host that
continually
may be expressed in the deeper layers of the skin
o Some mycotoxins are used to make drugs
- The agents causing these diseases are collectively
- Mycetismus
termed as DERMATOPHYTES , also known as
o occurs when poisonous mushrooms are eaten
Keratinophilic fungi because they produce the
o deadliest mushroom toxin is produced by the
extracellular enzymes, KERATINASE capable of
“death cap” mushroom
hydrolyzing keratin
o most mushrooms are not toxic but some produce
- Composed by members of three genera,
dangerous poisons
Microsporum, Trichophyton and Epidermophyton
o can cause neurological dysfunction,
hallucinations, organ damage, or death
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- Referred to as DERMATOPHYTOSIS or
RINGWORM or TINEA

D. SYSTEMIC MYCOSES

- Originate primarily in the lung and may spread to

many organ systems
- Primary focus of infection is the lung but secondary
infection may occur elsewhere in the body
- Inherently virulent
- Each species has biochemical and structural features
that enable it to evade host defense

OPPORTUNISTIC INFECTION
OPPORTUNISTIC MYCOSES

Infections in patients with immune deficiencies or in

C. SUBCUTANEOUS MYCOSES those people with impaired host defenses such as occurs
in AIDS, alteration of normal flora, Diabetes Mellitus,
- Infections involving the dermis, subcutaneous
immunosuppressive therapy, malignancy
tissues, muscle and fascia
- Initially involve the deeper layers of the dermis,
subcutaneous tissue or bone
- Most infections have a chronic or insidious growth
pattern, eventually extending into the epidermis and
are expressed clinically as lesions on the skin
surface
- Initiated by trauma to the skin and are difficult to
treat and surgical intervention (excision or
amputation) is frequently employed
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SUPERFICIAL MYCOSES
PITYRIASIS
TINEA NIGRA
WHITE PIEDRA
BLACK PIEDRA

Malassezia furfur (Disease: Pityriasis)

- Dimorphic lipophilic organism DISEASE:
- Does not attack the hair shaft, nails, or mucous Pityriasis versicolor, Pityriasis folliculitis, seborrhoeic
membranes. dermatitis and dandruff, neonatal pustulosis, blepharitis,
- May occur among immunocompromised/competent white piedra, Fungemia

ID: "spaghetti and meatballs" appearance of organism in TREATMENT:

skin scrapings Topical imidazole and oral ketoconazole or itraconazole
are commonly used for treatment of Pityriasis versicolor
 FINALS TOPIC 1 : MEDICAL MYCOLOGY 2017 || DR. KATH CALIGAGAN
Exophiala werneckii (Disease: Tinea nigra)
- Dematacious fungi (refers to the characteristic dark
appearance of fungi as it grows on agar)
- Halophilic
- Does not grow at 37°C
- Thick walled hyphae may form in aging colonies
ID: black yeast-like with 2 cells forming annellides
DISEASE:
Tinea nigra
superficial fungal infection of skin characterized by brown to
black macules which usually occur on the palmar aspects of
hands and occasionally the plantar and other surfaces of the skin
TREATMENT:
topical treatment with Whitfield's ointment (benzoic acid
compound) or an imidazole agent twice a day for 3-4 weeks is
effective
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Piedra hortai (Disease: Black Piedra)
- Dematacious fungi
- Found in soil particularly at tropical areas
- One of the keratinolytic fungi (produce a reddish brown
diffusable pigment)
ID: black nodule on hair shaft composed of ascostromata
DISEASE:
Black piedra
- characterized by formation of brown to black nodules that
are very firmly attached to the hair shaft. The nodules are
composed of ascostromata which are the fruiting body of
the fungus containing asci and ascospores.
- scalp hair is the most frequently infected area; most of the
cases are asymptomatic and may remain so for years;
mixed infections with Trichosporon may occur
TREATMENT:
- Shaving of affected hair, topical salycylic acid,
formaldehyde or azole creams are currently applied for
treatment of black piedra
- Oral ketoconazole or terbinafine may also be used
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Trichosporum beigelli (Disease: White Piedra) CUTANEOUS MYCOSES

- Normal flora of mouth, skin and nails DERMATOPHYTOSES
- Urease enzyme production is a significant feature of this CANDIDIASIS
genus

ID: white nodule on hair shaft composed of mycelia that

fragment into arthrospores or arthroconidia DERMATOPHYTOSES
DERMATOPHYTES
DISEASE: - Previously known as ringworm
White piedra - Have keratinase (keratinophilic) as major virulence
Infected hairs develop soft greyish-white nodules along the factor
shaft. Infections are usually localized to the axilla or scalp but - communicable and usually transmitted by contact
may also be seen on facial hairs and sometimes pubic hair.
White piedra is common in young adults.
ID:
TREATMENT: Microsporum spp.
Shaving of affected hair, topical salycylic acid, formaldehyde or Numerous multicelled macroconidia with thick, rough
azole creams are currently applied for treatment of black piedra walls; few unicellular microconidia
Topical application of an imidazole agent may prevent Epidermophyton spp.
reinfection microconidia absent; macroconidia are club-shaped, with
thin, smooth walls. Chlamydoconidia are usually also
present in older cultures
Trichophyton spp.
Few macroconidiathat are pencil-shaped and thin, with
smooth walls. 1-2 μ microconidia are usually abundant

DISEASE:
Dermatophytoses
Tinea or ringworm of scalp, glabrous skin, and nails
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Microsporum spp. Epidermophyton spp.
- Natural habitat is soil - Most common cause of tinea cruris
- Worldwide distribution - Worldwide distribution
- Mostly infect the hair and skin (except for M. persicolor - Man is the primary host
which does not infect hair)
- Nail infections are very rare
Two species:
Medically important species: E. flocossum (only specie pathogenic to man)
M. gypseum E. stockdaleae (nonpathogenic)
M. canis
ID: Microconidia absent; macroconidia are club-shaped
ID: Numerous multicelled ellipsoidal macroconidia with few multicelled with thin, smooth walls. Chlamydoconidia are
unicellular microconidia usually also present in older cultures
TREATMENT: TREATMENT:
Griseofulvin, oral therapy with terbinafine and itraconazole
Ketoconazole, Terbinafine and itraconazole
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Trichophyton spp.
- Inhabits the soil, humans or animals
- Requires nicotinic acid for growth

Two species:
T. mentagrophytes (most common cause of tinea pedis)
T. rubrum (most common cause of tinea ungium)

ID: Few macroconidia with smooth walls; Numerous

unicellular microconidia

TREATMENT:
Terbinafine and Itraconazole
Griseofulvin (used to be the DOC)
For treatment of tinea capitis and onychomycosis, oral
therapy is usually preferred

SUBCUTANEOUS MYCOSES
SPOROTHRICOSIS
CHROMOBLASTOMYCOSIS
PHAEOHYPOMYCOSIS
MYCETOMA TREATMENT:
Potassium iodide is one of the oldest therapeutic modalities used
for treatment of sporotrichosis Amphotericin B, ketoconazole,
SPOROTHRICOSIS and itraconazole are now more commonly used
Sporothrix schenkii
- Thermally dimorphic fungus
- Ubiquitous
CLINICAL FORMS:
- Occurs worldwide
- most common in tropical and subtropical regions
- endemic in Mexico, South Africa, and Japan
- Isolated from soil and plants
- Only specie pathogenic to man
- 75% of cases occur in males
- (increased exposure or X-linked)

DISEASE:
Sporotrichosis or Rose Gardener’s disease
subcutaneous infection with a common chronic and a rare
progressive course. The infection starts following entry of the
infecting fungus through the skin via a minor trauma, then the
infection may spread via the lymphatic route. Nodular
lymphangitis may develop
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Phialophora verrucosa
- Dematiaceous filamentous
- Inhabits the soil, plants, and decaying food
- Widely distributed in nature
- Principal causative agent of chromoblastomycosis

CHROMOBLASTOMYCOSIS
Phialophora verrucosa
Fonseca pedrosoi
Fonseca compacta
Cladosporium carionii
Rhinocladiella aquaspera

Sclerotic body or Muriform cell or Medlar body

Distinctive structure in infected tissues produce by all fungi
causing chromoblastomycosis.

These are dark brown (due to melanin), spherical thick-walled

structures with horizontal and vertical septa inside, found in
singly or in clusters, or within the giant cells.

DISEASE:
- Trauma in the skin
- Verrucous and wart-like over months to years extending along
draining lymphatics progressing to cauliflower-like nodules
with crusting abscesses
- “ Black-dots” on warty surface
- Rarely, Elephantiasis develops

TREATMENT:
- Oral itraconazole (as monotherapy or with oral flucytosine [5-
FC]), locally applied heat therapy, cryosurgery, and
combination therapy
- Relapse is common
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PAGE 16

Fonseca pedrosoi DISEASE:

- Dematiaceous filamentous - Vary from solitary encapsulated cysts in the subcutaneous
- Inhabits rotten wood and soil tissue
- to sinusitis
- to brain abscesses

TREATMENT:
- Itraconazole
- Flucytosine
- Amphotericin B

Cladosporium carionii
Elongated conidiophores with long, branching chains of oval
conidia
MYCETOMA

Madurella mycetomatis
Madurella grisea
Pseudallescheria boydii
Exiophiala jenselmei
Acromnium falciforme
PHAEOHYPOMYCOSIS
Wangiella dermatitidis
Exiophiala jeanselmei
Madurella spp.
- Dematiaceous filamentous fungus
Phialophora richradsiae
- Found in soil, particularly in tropical and subtropical
Bipolaris specifera
areas
- Has two species, M. mycetomatis and M. grisea
Wangiella dermatitidis
- Dematiaceous, cosmopolitan fungus
- Neurotropic fungus DISEASE:
- Inhabits the soil and plant material - Chronic, granulomatous disease of the skin and
- only species included in the genus subcutaneous tissue, which may involve muscle, bones, and
adjacent organs characterized by tumefaction, abscess
formation, and fistulae typically affects the lower extremities
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PAGE 17

(Madura foot), but it can occur in almost any region of the SYSTEMIC MYCOSES
body. COCCIDIOIDOMYCOSIS
- Enters the human body via trauma HISTOPLASMOSIS
- Progression is very slow which may take several years BLASTOMYCOSIS
PARACOCCIDIOIDOMYCOSIS
TREATMENT:
- Combination of antifungal and surgical therapy
- Ketoconazole or Griseofulvin for polonged durations of as
long as 8 to 24 months
FEATURES:
- Cause by thermally dimorphic fungi
- Exist in nature, soil
- Various geographic distribution
- Acquired by inhalation causing pulmonary infection
and ultimately dissemination
- No evidence of transmission among humans or
animals
- Otherwise healthy individuals are infected
- Uncommon
- Requires a large inoculum and a susceptible host
- Often occurs in endemic areas
- Most are asymptomatic and self-limiting
- In immune-compromised hosts, infections are more
often fatal

COCCIDIOMYCOSIS
Coccidioides immitis
- Thermally dimorphic fungus
- 37°C: Spherules filled with endospores
- 25°C: hyphae, barrel-shaped arthroconidia
- Isolated from soil and indigenous rodents
- Endemic in hot, semi-arid regions
- Peaks during summer and autumn, when dust is most
prevalent
- Considered to be the most virulent of fungal pathogens
- Inhalation of a single spore can initiate infection

CLINICAL FINDINGS:
- PRIMARY INFECTION
o Asymptomatic (60%)
o VALLEY Fever (40%)
 influenza-like illness fever, malaise, cough,
arthralgia, and headache
o Nodular lesions in lungs
o positive skin test in 2-4 weeks, remain for life
- SECONDARY (DISSEMINATED) INFECTION
(1%)
o Chronic/fulminant
o Infection of lungs, meninges, bones and skin,
GUT, cutaneous, ophthalmic

DIAGNOSIS:
- HISTOPATHOLOGY: spherules or endospores
seen in sputum, exudates or tissue
- CULTURE: SDA: Mould colonies at 25 °C
o Spherule production in vitro by incubation in an
enriched medium at 40°C, 20% CO2
- SEROLOGY: Complement fixation assay (in
cerebrospinal fluid), particle agglutination assay
- SKIN TEST: Coccidioidin and spheruline antigens,
Negative result may rule out the diagnosis
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- ANTIGEN: In HIV-infected patients with

disseminated histoplasmosis, histoplasma antigen
detection in serum and urine is at least 50%, and 90%
sensitive, respectively.

TREATMENT:
- Symptomatic treatment; not required for several cases
- Antifungal:
o Amphotericin B
o Itraconazole
- May be surgical resection of pulmonary lesions

TREATMENT:
- Symptomatic treatment (primary infection)
- Antifungal agents:
Amphotericin B
Itraconazole
Fluconazole(particularly for meningitis)

HISTOPLASMOSIS
Histoplasma capsulatum
- Thermally dimorphic fungus
o 37°C: Yeast cells in tissues
o 25°C: hyphae, microconidia, macroconidia,
tuberculate chlamydisphore
- Natural reservoir are soil, bat and avian habitats
- Inhalation of microconidia/primary cutaneous
inoculation
- May be prevalent all over the world, but the
incidence varies widely (most endemic in Ohio,
Mississipi, Kentucky)
- Eastern half of USA, most of Latin America, parts of
Asia, Europe, Middle East
- Variant var duboisii occurs in Africa BLASTOMYCOSIS
Blastomyces dermatitidis
CLINICAL FINDINGS: - Thermally dimorphic fungus
- PULMONARY INFECTION - 37°C: Yeast-like cells (~8 to 15 µm dia) have thick,
o Asymptomatic (95%) refractile walls with a broad budding base (4 to 5 µm
o May range from mild to severe to chronic dia) which remains attached to the parent cell,
cavitary lesions separating only when reaching the same size as the
- DISSEMINATED INFECTION parent.
o Rare, 1/200 - 25°C: Septate hyphae with relatively short
o RES (liver, spleen, lymph nodes, bone marrow) unbranched conidiophores
mucocutaneous infection o Conidia are hyaline (clear) and are produced
o Timely diagnosis requires a high index of singly at the apex of the conidiophore or can
clinical suspicion owing to the high mortality develop directly on the hyphae. Conidia are
associated with it. unicellular, round to pyriform (tear-drop) in
- PRIMARY CUTANEOUS INFECTION shape (~2 to 10 µm dia.) Conidia at the terminal
end of the conidiophore resemble a ‘lollipop’ in
DIAGNOSIS: structure.
- HISTOLOGY o Older cultures may produce thick-walled
- CULTURE of blood or bone marrow chlamydoconidia (7 to 18 µm dia.)
- SEROLOGY: Serological testing for antibody and - Most cases are in southern, central, and southeastern
histoplama antigen in blood and urine. USA
- Acquired by inhalation of conidia
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- Granulomatous mycotic infection that commonly

involves either the lungs and skin and spreads to
other organs

CLINICAL FINDINGS:
- ASYMPTOMATIC INFECTION
- PRIMARY CUTANEOUS INFECTION
o micro-abscesses lie just beneath the
epidermis, the outermost layer of the
skin, and are associated with a
granulomatous appearance of the PARACOCCIDIOMYCOSIS
surrounding skin Paracoccidiodes brasiliensis
- PULMONARY INFECTION - Thermally dimorphic fungus
o pulmonary lesions vary in size from - 37°C: Produces large yeast cells with multiple buds
granulomatous nodules to confluent, attached by narrow necks, giving the appearance of a
diffuse areas of pus-forming “mariner’s or ship’s wheel“
inflammation involving the entire lobe - 25°C: Presence of clamydospores and sometimes
of the lung oval or round conidia
- DISSEMINATED INFECTION o Under special culture-conditions aleurioconidia
o Skin, bone, GUT, CNS, spleen can be formed
- Most cases are Central and South America
DIAGNOSIS: - Acquired by inhalation of conidia
- DIRECT MICROSCOPY - A systemic chronic, granulomatous, and progressive
- CULTURE disease that mainly attacks the lungs, mucosa of the
- SEROLOGY: Immunodiffusion test and ELISA to mouth and nose, and neighboring teguments, with
detect antibodies to exoantigen A frequent spread to the lymph nodes, adrenal glands,
- SKIN TEST (BLASTOMYCIN ANTIGEN): and other viscera.
Limited/no diagnostic value
DIAGNOSIS:
TREATMENT: DIRECT MICROSCOPY
- Amphotericin B CULTURE
- Itraconazole SEROLOGY: Immunodiffusion test
- Fluconazole Complement fixation
- Corrective surgery
TREATMENT:
Amphotericin B
Itraconazole
Ketoconazole
Co-trimoxazole
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- Germ tubes
o Characteristic of Candida albicans (but may also
be seen with Candida dubinensis)
o Appear as outgrowths from the side of the yeast
cell after 2 to 3 hours of incubation in horse
serum

FORMS:
- SUPERFICIAL
o Thrush (patchy to confluent whitish
pseudomembrane in the tongue, lips, gums, palate)
o Vulvovaginitis (irritating, pruritic discharge)
OPPORTUNISTIC MYCOSES o Cutaneous Candidiasis (red moist vesicles)
CANDIDIASIS o Onychomycosis (painful erythematous swelling of
CRYPTOCOCCOSIS the nail fold with drumstick appearance
ASPERGILLOSIS - SYSTEMIC: Candidemia, Endocarditis, UTI
MUCORMYCOSIS - CHRONIC MUCOCUTANEOUS: Rare, early
PNEUMOCYSTIS childhood onset
PENICILLOSIS
DIAGNOSIS:
CANDIDIASIS - CULTURE
FEATURES: - DIRECT MICROSCOPY: Demonstration of budding
Not communicable yeast cell on KOH smear
Important sp:
TREATMENT:
Candida albicans Candida glabrata
For Superficial:
Candida tropicalis Candida guillermondii
Topical Nystatin , Oral Ketoconazole , Fluconazole
Candida parapsilosis Candida dubliniensis
For Systemic:
Amphotericin B + Oral Flucytosine/Fluconazole/
Caspofungin
RISK FACTORS:
AIDS
Pregnancy
DM
Young and old
Pills
Trauma (Burns, maceration)

Treatment with Cortocosteroids/ Antibiotics

Cellular immunodeficiency

Candida albicans
- Normal Flora
- Most common opportunistic and systemic mycosis
- Grows rapidly 3-4 days
- A yeast-like cell that divides by budding.
- The budding creates elongated cells which when
lined up may appear as a hyphae referred to as a
PSEUDOHYPHAE (false hyphae). Some true
hyphae may also be formed.
- Along side of the pseudohyphae, develops
BLASTOCONIDIA, which are budding yeast which
appear as small round ‘grape-like’ clusters
- Another structure is the CHLAMYDOSPORE,
which is thick walled, refractle usually develops at
the terminal end of the pseudohyphae
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- SEROLOGY: based on serological response to

capsular antigens.

TREATMENT:
Symptomatic
Amphotericin B + Oral Flucytosine
Fluconazole

CRYPTOCOCCOSIS
FEATURES:
Important species
Cryptococcus neoformans
Cryptococcus gattii

- Found with increasing frequency amongst HIV patients

and others who are immunocomprimised
o C. neoformans is the most common among
immunocompromised hosts while C. gattii is most
common in immunocompetent hosts.

Cryptococcus neoformans
- Only encapsulated yeast pathogenic to man
- Worldwide distribution
- Reservoir: Bird droppings (Pigeon)
- Mode of transmission: Inhalation of dessicated
yeast/smaller basidiospres
o Initially invades the RT, and disseminates in the
CNS, skin, bones and other tissues
ASPERGILLOSIS
- Rapidly growing round budding yeast (5-10µm) with
FEATURES:
polysaccharide capsule (thick non-staining)
Important species
- Produce whitish mucoid colonies 2-3 days at 37 °C
Aspergillus fumigatus (most common)
- (+) laccase (copper containing enzyme); (+) urease
A. flavus
- Do not produce pseudohyphae
A. niger
A. terreus
CLINICAL MANIFESTATIONS:
A. lentulus
- CHRONIC MENIGNITIS: Headache, Stiff neck,
disorientation; Fatal if untreated; NOT contagious MOT:
- Inhalation of conidia
- PRIMARY CRYPTOCOCCAL PNEUMONIA
- Transfer to wound via contaminated tape/bandages
- HEMATOGENOUS DISSEMINATION
- GENITOURINARY (PROSTATIC)
CRYPTOCOCCOSIS Aspergillus fumigatus
- Long conidiospores with terminal vesicles on which
- PRIMARY CUTANEOUS CRYPTOCOCCOSIS
phialides produce basipetal chains of conidia
- Cottony colonies
DIAGNOSIS:
- CULTURE
o Colonies producing capsules have glistening wet CLINICAL FORMS:
- ALLERGIC FORMS: Asthmatic reaction upon
or mucoid appearance
exposure
o Colonies without capsules have dull, creamy,
butyrous appearance - ASPERGILLOMA (fungus ball)
o Inhaled conidia enter preexisting cavities
- NEGATIVE STAINING MICROSCOPY:
Demonstration of encapsulated budding yeast cell
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o Previous Cavitary Disease (Tuberculosis, PNEUMOCYSTIS PNEUMONIA

sarcoidosis, Emphysema) FEATURES:
o Cough, dyspnea, weight loss, fatigue, hemoptysis - Caused by Pneumocystis jiroveci
- INVASIVE : Spread to GIT, kidney, liver, brain, - Pneumonia in immunosuppresed patients
other organs - Transmission: Aerosols

TREATMENT: Pneumocystis jiroveci

Amphotericin B - Formerly Pneumocystis carinii, a protozoa
Itraconazole - Ascomycetes
Voriconazole - Reservoir: Maybe an obligate member of the normal
Posaconazole flora
Surgery - Thick-walled cysts; spherical to elliptical 4-8 nuclei
- Thin-walled trophozoite
- Giemsa, Toluidine blue, Methamine silver, Calcoflour
white

TREATMENT:
Trimethoprim-Sulfamethoxazole
Pentamidine isethionate

MUCORMYCOSIS
FEATURES:
Important species
Rhizopus sp. PENICILLIOSIS
Rhizomucor sp. FEATURES:
Absidia sp. Important species
Cunninghamella sp. - Penicillium marneffei
Mucor sp. - Many species of Penicillium produce mycotoxins that
can either be detrimental or beneficial (eg.
CLINICAL FORMS: mycophenolic acid, rubratoxins
RHINOCEREBRAL MUCORMYCOSIS - (In 1928 that Alexander Flemming discovered that a
- Germination of the sporangiospores in the nasal culture of Penicillium rubens contained a substance
passages which inhibited certain bacteria, thus, the birth of
- Invasion of the hyphae into the blood vessels, causing antibiotic therapy)
thrombosis, infarction, and necrosis
THORACIC MUCORMYCOSIS Penicillium marneffei
- Inhalation of the sporangiospores with invasion of the - Ubiquitous fungus
lung parenchyma and vasculature - Capable of tolerating a
wide range of climates
TREATMENT: predominantly in
Aggressive surgical debridement regions that have a
Amphotericin B temperate climate such
Control underlying disease as Southeast Asia.
- Found in soils, decaying vegetation, grains and food
stuffs associated with bamboo rats
- Acquired thru inhalation of conidia
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- Thermally dimorphic fungus

- 37°C: Yeast-like cells CLINICAL MANIFESTATION:
- 25°C: It is capable of causing cutaneous infections as well as
o Septated, hyaline hyphae, about 1.5 µm to 5 µm in invading the spleen, liver and bones in
dia. immunocompromised and immunocompetent individuals
o Conidiophores can be simple or branched
described as monoverticillate, biverticillate or Culture on SDA.
terviticillate
o Phialides are flask or ampule in shape that produce
smooth or rough, single celled conidia (~2.5 µm to
5 µm) which extend as basipetal chains.
o Conidia can vary in shape from spherical to ovoid
to fusiform
o The entire structure, conidiophore and extending
- Most species exhibit rapid growth (5 days).
conidia resemble a ‘brush’ or penicillus (Latin),
- The surface is velvety to powdery.
from which the genus name was derived.
- The colony color varies with the species but is
usually a green, blue-green or grey-green, often with
Monoverticillate-
a white edge.
phialides extend
- The reverse usually a pale cream to yellow but may
directly from the
be a more intense reddish-brown.
hyphae
- An exception is P. marneffei which can produce a red
surface coloration that can diffuse into the medium.
Biverticillate-
phialides extend from
TREATMENT:
branches
- Amphotericin B
- Then Itraconazole
Terviticillate- phialides extend from structures called
- 90% mortality if without treatment
metulae, appearing as secondary branches, which extend
from primary branches extending from the hyphae which
extend from the hyphae

Characteristic “brush” or
“penicillus” (Latin)
appearance