GENERAL PROPERTIES,

CLASSIFICATION AND LABORATORY

DIAGNOSIS OF FUNGI
Mycology = study of fungi.
1st to appear than bacteria and viruses
Fungal infections = mycoses (sing., mycosis)
caused by certain yeasts, molds, and dimorphic fungi
2007 - only one fungal disease—
coccidioidomycosis—was classified as a nationally
notifiable infectious disease - 8,121 cases were
reported to the CDC in 2007
Eukaryotic organisms = many similarities to our
cells. Differences targeted by antifungals include:
1. Cell walls (CW).
 protect cells from osmotic shock, determine
cell shapes, and have components that are
antigenic.
 composed primarily of complex carbohydrates
- chitin with glucans and mannose. CW glucan
(not found in humans) = antifungal target of
the echinocandins like Caspofungin.
2. Ergosterol = dominant fungal membrane sterol
(rather than cholesterol) = targeted by
Imidazoles, Triazoles, and Polyenes antifungals.
Differences of Fungi From Bacteria
1. Possess rigid cell walls containing chitin,
mannan and other polysaccharides.
2. Cytoplasmic membrane contains sterols.
3. Cytoplasmic contents include
mitochondria and endoplasmic
reticulum.
4. Possess true nuclei with nuclear
membrane and paired chromosomes.
5. May be unicellular or multicellular.
 Differences of Fungi From
Bacteria

6. Divide asexually, sexually or by both.

7. Most are obligate or facultative aerobes.
8. Are chemotrophic.
9. Cells show various degrees of specialization.
Fungi grow in two basic forms, as yeasts
and molds.

Yeast: simplest type of fungus =

unicellular budding yeast, round to oval
shaped .= produced by budding
(blastoconidia).
Molds: Elongation of the cell =
produces a tubular, thread like
structure called hypha (hyphae –
plural)
• may be septate or non-septate.
Septae or septations = cross walls of
hyphae and occur in the hyphae of the
great majority of the disease-causing
fungi. They are referred to as septate.

Nonseptate or aseptate = lack

regularly occurring cross walls,
multinucleate and are also called
coenocytic= quite variable in width
with broad branching angles
General Properties of Fungi
Pseudohyphae (hyphae with sausage-like constrictions at
septations) = formed by some yeasts when they elongate but
remain attached to each other. Ex: Candida albicans
General Properties of Fungi
Thermally dimorphic fungi = capable of converting from a yeast or
yeast-like form to a filamentous form and vice versa (molds,yeast).
• Environmental conditions = temperature and nutrient
availability trigger changes.
• Exist in the yeast or a yeast-like form in a human and as the
filamentous form in the environment.‘ ‘Yeast beasts in body
heat; bold mold in the cold.’’
• Include the major pathogens: Blastomyces, Histoplasma,
Coccidioides, and Sporothrix in the United States and
Paracoccidioides in South and Central America.
General Properties of Fungi
Mycelium: tangled mass
of hyphae = form
mycelia are called molds
or filamentous fungi.
• divided into the
vegetative mycelium
and the aerial
mycelium.
General Properties of Fungi
Fungal spores = formed either
asexually or by a sexual process
involving nuclear fusion and then
meiosis. Fungal spores may be
used in identification.
• Conidia = asexual spores of
filamentous fungi (molds) or
mushrooms
Blastoconidia = new yeast ‘‘buds’’
Arthroconidia = conidia formed by
laying down joints in hyphae followed
by fragmentation of the hyphal strand
Fungal Nutrition
1. Saprobes = live on dead organic material.
2. Commensal colonizers = live in harmony on humans, deriving
their nutrition from compounds on body surfaces.
3. Pathogens = infect the healthy but cause more severe disease in
the compromised hosts. The damage to living cells provides
nutrition.
Fungi are placed in the phylum
Thallophyta. It is divisible into
two groups, algae and fungi.
Classification of Fungi
Algae: produce their own food by means
of chlorophyll possessed by them.

Fungi: do not possess chlorophyll =

saprophytes or parasites.
A. Morphological classification
B. Systematic classification.
A. Morphological Classification
1.Yeasts: round, oval or elongated
unicellular fungi. Most by asexual
process = budding = Some by fission.
Examples: Cryptococcus neoformans.

2. Yeast-like fungi: grow partly as yeast

and partly as elongated cells resembling
hyphae = pseudomycelium. Example:
Candida albicans.
A. Morphological Classification

3. Molds or filamentous fungi:

form true mycelia and
reproduce by the formation of
different types of spores.

Examples of molds:
Dermatophytes, Aspegillus,
Penicillium, Mucor and Rhizopus.
4. Dimorphic fungi: pathogenic to man
= yeast form in the host tissue and
in vitro at 37°C on enriched media
and hyphal (mycelial) form in vitro at
25°C.

Examples: Histoplasma capsulatum,

Sporothrix schenckii, Blastomyces
dermatitidis, Coccidioides immitis,
Paracoccidioides brasiliensis, and
Penicillium marneffei.
A. Morphological Classification
B. Systematic Classification
1. Mucormycetes (Formerly
Zygomycetes): Examples: Rhizopus,
absidia, mucor, pilobolus.

2. Ascomycetes: include both yeasts and

filamentous fungi.
B. Systematic Classification
3. Basidiomycetes: Examples: Mushrooms,
Filobasidiella neoformans (Cryptococcus
neoformans)

4. Deuteromycetes (Fungi imperfecti):

Most fungi of medical importance belong
to this class. Examples: Coccidioides
immitis, Paracoccidioides brasiliensis,
Candida albicans.
Reproduction and Sporulation
A. Sexual spores: Sexual spore is
formed by fusion of cells and
meiosis as in all forms of higher
life.
• 4 types—oospore, ascospore,
zygospore and basidiospore
Reproduction and Sporulation

B. Asexual spores: are produced by mitosis. May be

vegetative spores or aerial spores
I. Vegetative spores
• Blastospores: formed by budding from parent cell, as in
yeasts.
• Arthrospores: formed by the production of cross septa
into hyphae resulting in rectangular thick-walled spores.
• Chlamydospores: thick walled resting spores developed by
rounding up and thickening of hyphal segments.
Reproduction and Sporulation
B. Asexual spores:
II. Aerial spores
• Conidiospores: Spores borne
externally on sides or tips of
hyphae are called conidiophores or
simply conidia.
• Sporangiospores: formed within
the sporangium. They develop on
the ends of hyphae. Examples:
Mucor and Rhizopus.
Reproduction and Sporulation
B. Asexual spores:
II. Aerial spores
• Microconidia: small and
single, these are called
microconidia (unicellular).
• Macroconidia: large and
septate conidia and are
often multicellular.
Reproduction and Sporulation
• Teleomorph = form of the fungus producing sexual
spores
• Anamorph = form producing asexual spores
• Homothallic = self-fertile
• Heterothallic = mating types
Miscellaneous Terms
• Ascus = sac-like structure containing (usually eight)
ascospores developed during sexual reproduction in the
Ascomycetes.
• Asexual reproduction = spores (reproductive bodies of a
fungus) are formed directly from the vegetative
mycelium or from specialized hyphae.
• Chromoblastomycosis = subcutaneous mycosis often
the result of traumatic inoculation of a dematiaceous
fungus into the skin; etiologic agents include species of
Cladosporium, Fonsecaea, Exophiala, & Phialophora
Miscellaneous Terms
• Coenocytic = a cell or an aseptate hypha containing
numerous nuclei
• Conidiophore = a specialized branch of hypha on which
conidia are developed.
• Dematiaceous = pigmented, dark in color, usually gray
to black.
• Dermatophyte = fungi that cause superficial mycoses
• Diphasic (dimorphic) = ability of some fungi to grow as
either yeast or filamentous stages, depending on
conditions of growth
Miscellaneous Terms
• Ectothrixic = ability of the fungus to grow on the outside
of a hair shaft.
• Endothrixic = ability of the fungus to grow and
penetrate into the hair shaft.
• Endogenous = derived from internal source.
• Exogenous = derived from external source.
• Eukaryotes= organisms possessing a true nucleus (such
as fungi) as opposed to prokaryotes which do not
contain a nuclear membrane (such as bacteria).
• Fungemia= fungal blood infection
Miscellaneous Terms
• Fungi Imperfecti = a large class of fungi with septate
hyphae in which the asexual state of reproduction is
but not the sexual state. They are also called
Deuteromycetes and include the majority of medically
significant fungi.
• Germ Tube = small projections which arise from cells of
certain yeasts; indicates the onset of hyphal formation.
• Hyaline = colorless, clear.
• Mold = term generally referring to filamentous fungi
Miscellaneous Terms
• Mycetoma = a clinical syndrome of localized, tumorous
lesions in cutaneous and subcutaneous tissues due to
infections, often a foot, with actinomycetes or fungi.
• Mycosis = a disease caused by a fungus
• Mycotoxins= toxins of fungal origin
• Oospore = also called zygospore, a sexual spore
produced through the fusion of two unlike nuclei (class
Phycomycetes)
• Perfect fungi = fungi having sexual and asexual
reproductive stages
Miscellaneous Terms
• Phycomycetes = class of fungi forming a coenocytic
mycelium with stiff sporangiophores that bear
sporangiospores contained in a sporangium
• Pseudohyphae = - a chain of elongated budding cells
that have failed to detach (not true hyphae)
• Ringworm = term used to describe circular or ring-like
skin lesions produced by dermatophytes
• Rhizoids = root-like structures
• Saprobe (Saprophyte) = any plant organism that obtains
its nourishment from dead organic matter
Miscellaneous Terms
• Sporangiophore = a special aerial hypha or stalk bearing
a sporangium
• Sporangium = a sac or cell containing spores produced
asexually
• Spore = generally the reproductive body of a fungus;
occasionally, a resistant body for adverse environment
• Sterigmata = a specialized structure that arises from a
basidium and supports basidiospores
Classification of Mycoses (Fungal Infection)
Key Points:
• Mycology is the study of fungi
• The cell wall of fungi possesses two characteristic cell structures:
chitin and ergosterol
• Fungi grow in two basic forms, as yeasts and molds.
• Elongation of the cell produces a tubular, thread like structure
called hypha (septate or nonseptate).
• A tangled mass of hyphae constitutes the mycelium.
• Fungi which form mycelia are called molds or filamentous fungi
Key Points:
• The fungi are classified in the phylum Thallophyta.
• The phylum consists of four classes of fungi - Zygomycetes,
Ascomycetes, Basidiomycetes, and Deuteromycetes or Fungi
imperfecti
• The fungi can also be classified as yeast, yeast-like fungi, molds,
and dimorphic fungi depending on their morphology
• Infection caused by fungus is known as mycosis (plural mycoses).
Opportunistic Fungi
Patients with compromised host defenses, who are susceptible to
ubiquitous fungi, are referred to as opportunistic fungi.
Healthy people, if exposed to ubiquitous fungi are usually resistant.
Causative Fungal Agents
A. Yeast and yeast-like fungi: Cryptococcus, Candida spp.,
Torulopsis.
B. Filamentous fungi: Aspergillus, Mucor, Absidia,
Rhizopus, Cephalosporium, Fusarium, Penicil lium,
Geotrichum, Scopulariopsis.
C. Others: Pnuemocystis jiroveci.
A. YEAST AND YEAST-LIKE FUNGI
Candidiasis
Candidosis (candidiasis, moniliasis) - infection of the skin,
mucosa, and rarely of the internal organs, caused by a yeast-
like fungus Candida albicans, and occasionally by other
Candida species.
 Several species of the yeast genus Candida are capable of causing
candidiasis.
An opportunistic endogenous infection, the commonest
predisposing factor being diabetes.
Members of the normal flora of the skin, mucous
membranes, and gastrointestinal tract.
Species of Candida
Important species of Candida found in man are:
I. C. albicans;
II. C. stellatoidea;
III. C. tropicalis;
IV. C. krusei;
V. C. guilliermondii;
VI. C. parapsilosis;
VII. C. glabrata
VIII. C. viswanathii
 Pathogenesis
A. Superficial
(cutaneous or
mucosal)
candidiasis
B. Systemic
candidiasis
C. Superficial
(cutaneous or
mucosal)
candidiasis
A. Superficial (cutaneous or
mucosal) Candidiasis
A. Superficial (cutaneous or mucosal)
Candidiasis
A. Mucocutaneous Lesions
1. Oral thrush: can occur on the
tongue, lips, gums or palate.
 Found commonly in bottle-fed infants
and the aged and debilitated.
 Creamy white patches appear on the
tongue or buccal mucosa, that leave a
red oozing surface on removal.
A. Mucocutaneous Lesions
2. Vulvovaginitis
3. Balanitis
4. Conjunctivitis
5. Keratitis.
Other Presentation of Candidiasis

• Pseudomembranous type- reveals a

raw bleeding surface when scraped;
• Erythematous type—flat, red,
occasionally sore areas;
• Candida leukoplakia—nonremovable
white thickening of epithelium
caused by candida spp
• Angular cheilitis—sore fissures at the
corners of the mouth.
B. Skin and Nail Infections
Intertriginous infection: occurs in
moist, warm parts of the body
such as the axillae, groin, and
intergluteal or inframammary
folds.
Interdigital involvement:
between the fingers follows
repeated prolonged immersion in
water
Onychomycosis: Candidal
invasion of the nails and around
the nail plate
Napkin dermatitis in infants
Systemic Candidiasis
1. Intestinal candidiasis: a frequent sequel to oral antibiotic therapy and may
present as diarrhea not responding to treatment.
2. Bronchopulmonary candidiasis - form of pulmonary fungal infection and
refers to an opportunistic infection of the lung with the fungus Candida
albicans.

3. Septicemia
4. Endocarditis
5. Meningitis
6. Kidney infections
7. Urinary tract infections
Chronic Mucocutaneous Candidiasis
Most forms have onset in early
childhood
Associated with cellular
immunodeficiencies and
endocrinopathies, and result in
chronic superficial disfiguring
infections of any or all areas of skin
or mucosa.
Treatment
Management is mainly by removing the predisposing causes.
All Candida strains are sensitive to Nystatin.
Mucosal and cutaneous infections - number of different topical
creams, lotions, ointments, and suppositories containing various
azole antifungal agents
Oral systemic therapy - accomplished with either fluconazole or
itraconazole.
Bladder colonization or cystitis - instillation of amphotericin B directly
into the bladder (bladder wash) or by oral administration of
fluconazole.
More deep-seated infections require systemic therapy oral
fluconazole
A. YEAST AND YEAST-LIKE FUNGI
Cryptococcosis
• Known as Torulosis, European Blastomycosis, Busse–buschke
Disease
• Is subacute or chronic infection caused by the capsulate yeast
cryptococcus neoformans.
• Most frequently recognized as a disease of the central nervous
system (CNS), although the primary site of infection is the lungs.
• Disease occurs sporadically throughout the world but it is now
seen most often in patients with AIDS.
Adsorbed antisera have defined five serotypes:

•(A–D and AD) and three varieties

• C. neoformans vargrubii (serotype A),
•C. neoformans var neoformans (serotype D),
•C. neoformans vargattii (serotype B or C)
•Most infections are caused by C.neoformans var.
neoformans - found in the excreta of wild and
domesticated birds throughout the world.
Cryptococcosis
Is worldwide in distribution
Bird droppings - pigeon droppings- enrich for the growth
of C. neoformans - serve as a reservoir of infection.
 Organism grows luxuriantly in pigeon excreta.
 Birds do not appear to become infected, probably because of
their high body temperature.
In addition to patients with AIDS or hematologic
malignancies, patients being maintained on
corticosteroids are highly susceptible to cryptococcosis.
Cryptococcosis
Infection is by inhalation but may sometimes be through skin or
mucosa
Primary pulmonary infection may be asymptomatic or may
mimic an influenza-like respiratory infection - resolving
spontaneously
Pulmonary cryptococcosis may lead to a mild pneumonitis.
• Compromised patient - yeasts may multiply and disseminate to other
parts of the body
• Central nervous system - cryptococcal meningoencephalitis.
• Include the skin, eye, and prostate gland.
Cryptococcal meningitis
Is the most serious type of infection
Resemble tuberculous or other chronic types of
meningitis.
Predominantly a disease of the CNS, lesions of the skin,
mucosa, viscera and bones may also occur.
Visceral forms simulate tuberculosis and cancer clinically.
Bones and joints may be involved
Cutaneous cryptococcosis varies from small ulcers to
large granulomas.
Treatment
• Combination therapy of amphotericin B and flucytosine
has been considered the standard treatment for
cryptococcal meningitis.
• Fluconazole offers excellent penetration of the central
nervous system.
A. YEAST AND YEAST-LIKE FUNGI
Aspergillus species
• Are ubiquitous saprophytes in
nature, and aspergillosis occurs
worldwide.
• Most important species are A. A. Niger
A. Flavus
fumigatus, A. niger, A. flavus, A.
terreus and A. nidulans.

A. nidulans

A. fumigatus
A. terreus
Aspergillus species
• Atopic individuals often develop severe allergic reactions to the
conidial antigens.
• Immunocompromised patients, the conidia may germinate to
produce hyphae that invade the lungs and other tissues.
A. Localized infections
• Sinusitis: A. flavus and A.
fumigatus.
• Mycotic keratits: A. flavus
and A. fumigatus.
• Otomycosis: A niger.
B. Systemic aspergillosis - Pulmonary
aspergillosis
• Allergic asthma: development of IgE antibodies to the
surface antigens of aspergillus conidia elicits an
immediate asthmatic reaction upon subsequent
exposure.
• Bronchopulmonary aspergillosis: conidia germinate and
hyphae colonize the bronchial tree without invading the
lung parenchyma -phenomenon is characteristic of allergic
bronchopulmonary aspergillosis.
B. Systemic aspergillosis - Pulmonary
aspergillosis
• Colonizing aspergillosis
(aspergilloma): develops in
preexisting pulmonary cavities,
such as in tuberculosis or cystic
disease- referred to as fungus
ball.
• The fungus grows into large ‘balls’
(aspergilloma). Cases of
aspergilloma rarely become
invasive.
B. Systemic aspergillosis - Invasive
aspergillosis:
• Form occurs in severely
immunocompromised
individuals.
• Disseminated aspergillosis
involving the brain, kidney
and other organs is a fatal
complication.
 B. FILAMENTOUS FUNGI
Mucormycoses (Zygomycosis)
Mucormycoses
• leading pathogens among this group of fungi are species
of the genera Rhizopus, Rhizomucor, Absidia,
Cunninghamella and Mucor.
• Fungi are ubiquitous, thermotolerant saprophytes.
Clinical Varieties of Mucormycosis
Rhinocerebral mucormycosis:
a rapidly fulminating infection.
• from germination of the
sporangiospores in the nasal
passages and invasion of the
hyphae into the blood vessels.
• can progress rapidly with
invasion of the sinuses, eyes,
cranial bones and brain.
Clinical Varieties of Mucormycosis
• Thoracic mucormycosis: follows inhalation of the
sporangiospores with invasion of the lung parenchyma
and vasculature.
• Other sites of invasion: Primary cutaneous infections
have also been reported, but these are extremely rare.
Subcutaneous forms of zygomycosis are less serious.
Treatment
• Aggressive surgical debridement
• Rapid administration of amphotericin B
• Control of the underlying disease.
B. FILAMENTOUS FUNGI
Penicilliosis
 Talaromycosis (Penicilliosis)
T. marneffei used to be called Penicillium
marneffei, and talaromycosis used to be
called penicillios
more than 150 known species of the genus
Penicillium - are caused by Penicillium
marnefei.
 causes penicillosis, keratitis, otomycosis and
rarely deep infections.
 causes serious disseminated disease with
characteristic papular skin lesions in AIDS
patients in SouthEast Asia.
Talaromycosis (Penicilliosis)
Cutaneous lesions and subcutaneous
abscesses have been reported.
Bumps on the skin are a common
symptom - usually small
Healthy people rarely get talaromycosis
Itraconazole - most commonly used
medicine - but healthcare providers also
can prescribe other antifungal medicines.
C. OTHER FUNGAL AGENTS
Pneumocystis jiroveci
Pneumocystis jiroveci
• Until recently, P. jeroveci was thought to be a protozoan.
• Molecular studies indicate that Pneumocystis carinii is a fungus with a
close relationship to ascomycetes.
• used to be called Pneumocystis carinii - some people considered using
the abbreviation “PJP,” but to avoid confusion, Pneumocystis jirovecii
pneumonia is still abbreviated “PCP.

• P. carinii has three stages:

• Trophozoites thin walled (1–4 μm).
• Precyst: It is 5–8 μm.
• Cysts: Cysts are thick-walled and spherical (4–6 μm) and contains 4 to 8
nuclei.
Pneumocystis pneumonia
• P. jiroveci is normally a
commensal in the lung,
spread by respiratory
droplets.
• Immunocompetent
individuals, infection is
asymptomatic.
• imunocompromised
patients, serious life-
threatening pneumonia can
develop
Pneumocystis pneumonia
• The multiplication of the parasite
in the lungs induces a hyaline or
foamy alveolar exudate
• Stained sections, the exudate
filling the alveoli shows a
characteristic honeycomb pattern
• Chest radiographs may be normal
or show a diffuse interstitial
infiltrate.
Treatment
• There is no vaccine to prevent PCP
• Acute cases of pneumocystis pneumonia are treated with
trimethoprim-sulfamethoxazole (TMP-SMZ) or pentamidine
isethionate.
• Prophylaxis can be achieved with daily TMP-SMZ or aerosolized
pentamidine.
OTHER OPPORTUNISTIC FUNGI
Otomycosis
Others
• Fusarium species, Trichosporon beigelii and Pseudallescheria
boydii have been reported.
• Diagnosis is made by culture of the causative organism from
clinical specimens and serological tests play little part.
Otomycosis
• fungal infection of the external ear
• very common disease and is usually caused
by species of A. niger, A. fumigatus,
Penicillium, Candida albicans, C. tropicalis
and C. krusei.
• symptoms are itching, pain and deafness
• Secondary bacterial infection- due to
Pseudomonas and Proteus, causes
suppuration.
• Diagnosis can be made by demonstration of
the fungi in scrapings and by culture.
OTHER OPPORTUNISTIC FUNGI
Keratomycosis (Mycotic Keratitis or
Fungal Keratitis)
Keratomycosis
• Mycotic or fungal keratitis
• Invasive fungal infection of the cornea, secondary to injury,
bacterial infection and treatment with antibacterial agents and
steroids.
• Occur most often in hot climates and are caused by common
saprophytic molds.
• Frequently caused by a. Fumigatus, A. Flavus, A. Glaucus and A.
Niger. In addition, species of fusar ium, curvularia, candida,
acremonium, paecilomyces, penicillium, alternaria, fonsecea,
pseudallescheria, drechslera and aureobasidium
Key Points
• Patients with compromised host defenses, which are susceptible
to ubiquitous fungi, are referred to as opportunistic fungi.
• Candida albicans, Aspergillus fumigatus, Aspergillus niger,
Penicillium sp., Rhizopus and Mucor are some examples of
opportunistic fungi
Candidiasis
• Candidosis (candidiasis, moniliasis) is an infection of the skin,
mucosa, and rarely of the internal organs, caused by a yeast-like
fungus Candida albicans, and occasionally by other Candida species.
• It causes (a) Mucocutaneous lesions (Oral thrush); 2. Vulvovaginitis,
conjunctivitis keratitis; Skin and nail infections
Cryptococcosis
Cryptococcosis is caused by the capsulate yeast Cryotococcus
neoformans
C. neoformans causes: Pulmonary cryptococcosis in
immunocompromised hosts. Central nervous system (CNS)
cryptococcosis.
Disseminated nonpulmonary non-CNS cryptococcosis

Aspergillosis
Aspergillus species most frequently involved in human infections
are A. fumigatus, A. flovus and A. niger
In immunocompetent hosts, Aspergillus species may primarily
affect thelungs causing four main syndromes including allergic
bronchopulmonary aspergillosis, chronic necrotizing aspergillus
pneumonia, aspergilloma and invasive aspergillosis
Zygomycosis
• Zygomycosis (mucormycosis or phycomycosis) is an infection
caused by saprophytic molds of the class Zygomycetes (mainly
Mucor, Rhizopus and Absidia)
• Zygomycetes can cause rhinocerebral zygomycosis, pulmonary
zygomycosis and gastrointestinal zygomycosis

Pneumocystis jiroveci
• Pneumocystis jiroveci, is the causative agent of Pneumocystis
carinii pneumonia (PCP).
• Transmission of infection occurs by inhalation
• PCP is the most common opportunistic infection in HIV-
patients
Otomycosis
• is a fungal infection of the external ear
• usually caused by species of A. niger, A. fumigatus, Penicillium,
Candida albicans, C. tro picalis and C. krusei
Keratomycosis
• or mycotic or fungal keratitis
• most frequently caused by A. fumigatus, A. flavus, A. glaucus and
A. niger.
Superficial, Cutaneous and Subcutaneous Mycoses
 SUPERFICIAL MYCOSES
Limited to the outer most layers of the skin and
hair.
Elicit little or no host immune response and are
nondestructive - asymptomatic.
Usually of cosmetic concern only and are easy to
diagnose and treat.
1. Infection of skin: caused by Malassezia furfur
(Pityriasis versicolor) and Exophiala werneckii
(Tinea nigra)
2. Infection of hair: caused by Piedraia hortae
(Black piedra) and Trichosporon beigelii
(white piedra).
 Pityriasis versicolor (Tinea versicolor)
 Chronic, usually asymptomatic
 Involvement of the stratum corneum
 Characterized by discrete or confluent macular areas of discoloration or depigmentation of
the skin.
 Areas involved are mainly the chest, abdomen, up per limbs and back.
 The disease is worldwide in distribution - 60% of the population.
 Causative agent: a lipophilic, yeast-like fungus Pityrosporum orbiculare (Malassezia furfur).
 Infection is thought to result from the direct or indirect transfer of infected keratinous
material from one person to another.
 Small hypopigmented or hyperpigmented macules lesions - upper trunk, arms, chest,
shoulders, face, and neck are most often involved, but any part of the body may be affected
 Tends to interfere with melanin production, lesions are hypopigmented in darks skinned
individuals
 Light-skinned individuals, the lesions are pink to pale brown
Tinea Versicolor- Treatment
 Use of topical azoles or selenium sulfide shampoo.
 For more widespread infection, oral ketoconazole or itraconazole may be
used.

Tinea Nigra
 Or tinea nigra palmaris
 A localized infection of the stratum corneum, particularly of the palms
 Solitary, irregular, pigmented (brown to black) maculeis
 Caused by the dematiaceous fungus hortaea (formerly exophiala werneckii)
werneckii.
 Lesion grossly may resemble a malignant melanoma, biopsy or local excision
may be considered - simple microscopic examination of skin scrapings
 Tinea Nigra
Likely contracted by traumatic inoculation of the fungus into the
superficial layers of the epidermis.
Most prevalent in Africa, Asia, and Central and South America.
Children and young adults are most often affected, with a higher
incidence in females.
no scaling or invasion of hair follicles, and the infection is not
contagious.
Responds well to topical therapy, including Whitfield ointment,
azole creams, and terbinafine.
 White Piedra
• Characterized by the appearance of firm, irregular nodules along the hair shaft.
– White piedra caused by Trichosporon beigelii, axillary, pubic, beard, and scalp hair may
be infected
– Also caused by yeastlike fungi of the genus Trichosporon: T. inkin, T. asahii, or T.
mucoides

Piedra
• Occurs in tropical and subtropical regions - related to poor hygiene
• Affects the hairs of the groin and axillae (mustaches and beards, on eyelashes and
eyebrows, and in armpit and pubic hair)
• Surrounds the hair shaft and forms a white to brown swelling along the hair strand.
 Swellings are soft and pasty and may be easily removed by running a section of the hair
between the thumb and forefinger.
• Infection does not damage the hair shaft.
 Piedra - Treatment
• Use of topical azoles
• Improved hygiene and shaving of the infected hair are also
effective and usually negate the necessity of medical treatment.
• Topical azoles – Clotrimazole, Miconazole, Econazole, Oxiconazole,
Sertaconazole, Terconazole, Sulconazole, Tioconazole,
Butoconazole
 Black Piedra
• Piedraia hortae , hard nodules up to 1 mm in diameter, mainly on the
hairs of the scalp
• Grows as pigmented (brown to reddish black) mold.
• As the culture ages, spindle-shaped ascospores are formed within
specialized structures (asci).
• These structures (asci and ascospores- sexual phase of the fungus) -
produced within the rock-hard hyphal mass that surrounds the hair
shaft.
• Uncommon and has been reported from tropical areas in Latin
America and Central Africa.
• Thought to be a condition of poor hygiene
• Treatment - accomplished by a haircut and proper, regular washings.
 CUTANEOUS MYCOSES
Infections that extend deeper into the epidermis as well
as invasive hair and nail disease.
1. Infection of skin, hair and nail infections caused by
dermatophytic fungi (dermatophytosis) and non-
dermatophytic fungi (dermatomycosis).
2. Infection of skin, nail and mucous membrane caused by C.
albicans and other Candida species.
 Dermatophytes
• Group of closely related filamentous fungi that infect
only superficial keratinized tissues—the skin, hair and
nails.
• Among the most prevalent infections in the world.
• Various forms of dermatophytosis are referred to as
“tineas” or ringworm.
• About 40 species of dermatophytes are known to cause
infection in humans and animals.
• Restricted to the nonviable skin because most are
unable to grow at 37°c or in the presence of serum.
 Dermatophytes- Tinea
Tineas are classified according to the anatomic site or structure
affected:
1. Tinea capitis of the scalp, eyebrows, and eyelashes;
2. Tinea barbae of the beard;
3. Tinea corporis of the smooth or glabrous skin;
4. Tinea cruris of the groin;
5. Tinea pedis of the foot;
6. Tinea unguium of the nails (also known as onychomycosis)
 Dermatophytes - Genera
1. Trichophyton: infect hair, skin or nails.
2. Microsporum: infect only hair and skin.
3. Epidermophyton: attacks the skin and nails but not the hair.
Dermatophytes - Classification depending on habitat:

1. Anthropophilic species: Human beings are the main or only

hosts, may be transmitted directly or indirectly from person to
person
– T. rubrum, M. audouinii and Epidermophyton floccosum.
2. Zoophilic species: parasitize the hair and skin of animals but can
be transmitted to humans
– T. verrucosum in cattle and M. canis in dogs and cats.
3. Geophilic species: live in the soil and are occasional pathogens of
both animals and humans, less pathogenic for human beings
– M. gypseum and T. ajelloi.
 Dermatophytes - Pathogenicity
• Grow only on the keratinized layers of the skin and its
appendages - do not ordinarily penetrate the living tissues.
• Lesions vary - site of the infection and the species of fungus
involved.
• Hypersensitivity to fungus antigens - play a role in pathogenesis
and is probably responsible for the sterile vesicular lesions -
sometimes seen in sites distant from the ringworm- are called
dermatophytids (or ‘id’ reaction).
• Hypersensitivity can be demonstrated by skin testing with the
fungus antigen - Trichophytin.
 Types of Hair Infection (10% KOH wet mounts)
1. Ectothrix: arthroconidia are formed on
the outside of the hair - M. audouinii,
M. canis and T. mentagrophytes
2. Endothrix: arthroconidia are formed
inside the hair - T. tonsurans and T.
violaceum
3. Favus (Favic) : hyphae, arthroconidia,
and empty spaces resembling air
bubbles (“honeycomb” pattern) are
formed inside the hair - T. schoenleinii
 Clinical Findings
• Dermatophyte infections were
mistakenly termed ring worm or
tinea.
• Tinea capitis is more common in
prepubescent children, and tinea
cruris and tinea pedis are primarily
diseases of adult males
• On a worldwide scale, T. rubrum
and T. mentagrophytes account for
80% to 90% of all
dermatophytoses
Clinical Forms (Site of Involvement)
 Tinea corporis (Tinea glabrosa): ringworm of the smooth or non-hairy skin of the
body , characterized by extensive concentric rings of papulosquamous scaly
patches.
 Tinea cruris or jock itch: occurs in the groin and the perineum.
 Tinea manus: Ringworm of the hands or fingers.
 Tinea barbae or barber’s itch: involvement of the bearded areas of the face and
neck.
 Tinea pedis or athletes’ foot: ringworm of the foot.
 Tinea unguium (onychomycosis): Nail infection may follow prolonged tinea pedis.
 Tinea capitis: Ringworm of the scalp and hair.
 Favus: a chronic type of ringworm in which dense crusts (scutula) develop in the
hair follicles, which lead to alopecia and scarring.
 Kerion: Scalp infection sometimes produces severe boggy lesions with marked
inflammatory reaction called kerion.
 Epidemiology , Treatment and Prevention
• Occurs throughout the world
• Rare in the tropics where most walk barefoot
• In India, Tinea capitis occurs more often in the native children than
in Europeans.
• Topical therapy is satisfactory for most skin infections- include
azole compounds, terbinafine, amorolfine and ciclopirox olamine.
• Oral griseofulvin is useful for scalp, skin and fingernail infections.
• Relatively little has been done to control the spread of ringworm.
 Onychomycosis Caused by Non-dermatophytic Fungi
• Scopulariopsis brevicaulis, Scytalidium
dimidiatum, Scytalidium hyalinum, and a
variety of others, including Aspergillus,
Fusarium, and Candida species
• S. brevicaulis and Scytalidium spp. are proven
nail pathogens
• S. brevicaulis, S. dimidiatum, and S. hyalinum
are notoriously difficult to treat because they
are not usually susceptible to any antifungals.
Onychomycosis Caused by Non-dermatophytic Fungi

• Partial surgical removal of infected nails, coupled with

oral itraconazole or terbinafine or intensive treatment
with 5% amorolfine nail lacquer or
• Whitfield ointment, may be useful in achieving a clinical
response.
SUBCUTANEOUS MYCOSES
Introduced traumatically through the skin - deeper layers of the
dermis, subcutaneous tissue, and bone - rarely spread to distant
organs
Chronic and insidious; once established, the infections are
stubborn to most antifungal therapy
Main fungal infections include lymphocutaneous sporotrichosis,
chromoblastomycosis, eumycotic mycetoma, subcutaneous
zygomycosis, and subcutaneous phaeohyphomycosis.
Lymphocutaneous sporotrichosis is caused by a single fungal
pathogen, Sporothrix schenckii, the other subcutaneous mycoses
are clinical syndromes caused by multiple fungal etiologies
Causative agents of subcutaneous mycoses are generally
considered to have low pathogenic potential and are
commonly isolated from soil, wood, or decaying vegetation.
Exposure is largely occupational or related to hobbies (e.g.,
Gardening, wood gathering)
 Lymphocutaneous Sporotrichosis
• Caused by S. schenckii - dimorphic fungus -ubiquitous in
soil and decaying vegetation.
• Infection is chronic - characterized by nodular and
ulcerative lesions that develop along lymphatics that drain
the primary site of inoculation
Phaeohyphomycosis - term applied to infections characterized
by the presence of darkly pigmented septate hyphae in tissue
• Dissemination sites - bones, eyes, lungs, and central
nervous system, is extremely rare (<1% of all cases)
 Lymphocutaneous Sporotrichosis
• Usually sporadic and is most common in warmer climates
• Outbreaks - related to forest work, mining, and gardening
have occurred.
• Classic infection is associated with traumatic inoculation
of soil or vegetable or organic matter contaminated with
the fungus
• Zoonotic transmission - reported in armadillo hunters
and in association with infected cats.
 Lymphocutaneous Sporotrichosis
• Classic treatment - oral potassium iodide in saturated
solution
• Itraconazole has been shown to be safe and highly
effective at low doses and is the current treatment of
choice
• Fluconazole should be used only if the patient cannot
tolerate these other agents
• The local application of heat has also been shown to be
effective.
 Mycetoma
• Divided into three types,
Eumycetomas, Actinomycetomas
and Botryomycosis.
• A similar condition called
‘botryomycosis’ is caused by
staphylococcus aureus and some
other bacteria.
 Eumycotic Mycetoma
• Caused by true fungi - as opposed to Actinomycotic mycetomas-
caused by aerobic actinomycetes (bacteria)
• A chronic, granulomatous infection of the skin, subcutaneous
tissues, fascia and bone - often affects the foot or the hand.
• The disease was originally reported by Gill (1842) from Madurai,
South India, and Carter (1860) established its fungal etiology - -
known as Maduramycosis or Madura foot.
• Occurs worldwide - most prevalent in tropical and subtropical
regions of Africa, Asia and Central America. In India, it is quite
common in Tamil Nadu but rare in Kerala.
 Eumycotic Mycetoma
• Formation of multiple granulomas and abscesses - large
aggregates of fungal hyphae known as granules or grains
contain cells that have marked modifications of internal and external
structure, ranging from reduplications of the cell wall to the formation
of a hard, cement-like extracellular matrix
• Etiologic agents encompass a wide range of fungi, including
Phaeoacremonium, Curvularia, Fusarium, Madurella, Exophiala,
Pyrenochaeta, Leptosphaeria, and Scedosporium species
• Fungi differ from country to country, and the agents that are
common in one region are rarely reported from others
 Mycetoma
• Management is difficult - surgical debridement or excision and
chemotherapy.
• Actinomycetoma responds well to rifampicin in combination
with sulfonamides or cotrimoxazole
• Promising treatment responses have recently been reported for
terbinafine, voriconazole, and posaconazole.
 Chromoblastomycosis
• Also known as chromomycosis - chronic, localized disease of the
skin and subcutaneous tissues.
• Etiological agents are soil inhabiting fungi of the family
Dematiaceae.
• All are dematiaceous fungi which are darkly pigmented fungi.
These include: Phialophora verrucosa, Fonsecaea pedrosoi,
Rhinocladiella aquaspersa, Fonsecaea compacta, and Cladophialophora
carrionii.
• Enter the skin by traumatic implantation - lesion develops slowly
around the site of implantation.
Chromoblastomycosis
• Mainly encountered in the tropics -coupled with the lack of
protective footwear and clothing
• Characterized by the slow development of progressive
granulomatous lesions that in time induce hyperplasia of the
epidermal tissue.
• Infections appear as multiple, large, warty, “cauliflowerlike”
growths that are usually clustered within the same region
• Squamous cell carcinomas may develop in longstanding
lesions
Chromoblastomycosis

• Antifungal therapy is often ineffective because of the advanced

stage of infection upon presentation.
• Drugs that appear to be most effective are itraconazole and
terbinafine
• Recently, posaconazole has been used with modest success
often combined with flucytosine
 Subcutaneous Entomophthoromycosis
• Known as subcutaneous mucormycosis
• Caused by mucormycetes of the order Entomophthorales:
Conidiobolus coronatus and Basidiobolus ranarum (haptosporus)
• Cause a chronic subcutaneous form of mucormycosis that occurs
sporadically as a result of traumatic implantation of the fungus
• B. ranarum causes subcutaneous infection of the proximal limbs in
children
• C. coronatus infection is localized to the facial area, predominantly in
adults
 Subcutaneous Entomophthoromycosis
• Both are saprophytes that are present in leaf and plant debris
• B. ranarum - been found in the intestinal contents of small reptiles and
amphibians
 have disk shaped, rubbery, movable masses that may be quite large and are localized to
the shoulder, pelvis, hips, and thighs
• C. coronatus infection is confined to the rhino facial area and often does not
come to medical attention until there is a noticeable swelling of the upper lip
or face
• Both may be treated with itraconazole.
• Alternatively, oral potassium iodide in saturated solution has been used.
• Facial reconstructive surgery may be necessary in the case of C. coronatus
infection; extensive fibrosis remains after eradication of the fungus.
Subcutaneous Phaeohyphomycosis
• Term used to describe a heterogeneous array of fungal
infections caused by pigmented, or dematiaceous, fungi which
are present in tissue as irregular hyphae
• Caused by a wide range of fungi, all of which exist in nature as
saprophytes of soil, wood, and decaying vegetation.
• Most frequent etiologic agents – Exophiala, Jeanselmei,
Alternaria, Curvularia, Phaeoacremonium, and Bipolaris spp.
• Wood splinters have been found in histopathologic material,
suggesting the mode of inoculation
 Subcutaneous Phaeohyphomycosis

• Lesions generally occur on the feet and legs, although the hands and other body
sites may be involved.
• Lesions grow slowly and expand over a period of months or years
• Firm or fluctuant and are usually painless
• Main treatment is surgical excision.
• Plaque-like lesions generally respond to treatment with itraconazole with or
without concomitant flucytosine.
• Posaconazole, voriconazole, and terbinafine may also be active against these
groups of fungi.
 Rhinosporidiosis
• Chronic granulomatous disease - development of large polyps or
wart-like lesions in the nose, conjunctiva and occsasionally in ears,
larynx, bronchus, penile urethra, vagina, rectum and skin.
• More than 90% of the cases have been reported from India,
Srilanka and South America.
• Causative fungus Rhinosporidium seeberi
• Mode of infection is not known - is believed to originate from
stagnant water or aquatic life.
• It is believed that fish may be the natural hosts of R. seeberi.
• Superficial Mycoses Key Points
 Pityriasis versicolor or tinea versicolor is caused by Malassezia furfur (Pityrosporum
orbiculare)
 Tinea nigra is an infection of keratinized layer of skin caused by Hortaea (Exophiala)
werneckii
 Black piedra is a superficial infection of the hair caused by Piedroiohortae -
dematiaceous fungus
 White piedra is an infection of the hair caused by yeast-like organism, Trichosporon
beigelii
• Cutaneous Mycoses
 The dermatophytes infect only superficial keratinized structure such as skin, hair and
nail but not deeper tissues
 Dermatphytes belong to three genera: Trichophyton, Microsporum and Epidermophyton
 Clinical findings: Dermatophyte infections were mistakenly termed ring worm or tinea
because of the raised circular lesions
 Laboratory diagnosis is based on microscopy and culture. The differentiation of the three
genera is based mainly on nature of macroconidia
• Subcutaneous Mycosis
 Mycetoma is a chronic, granulomatous infection of the skin, subcutaneous tissues,
fascia and bone, which most often affects the foot or the hand
 It can be divided into three types, eumycetomas, actinomycetomas and
botryomycosis
 Chromoblastomycosis or chromomycosis is caused by fungi collectively called
dematiaceous fungi
 Sporotrichosis is caused by Sporothrix schenckii, a saprophyte in nature
• Subcutaneous Mycosis
 Rhinosporidiosis is a chronic granulomatous disease characterized by the
development of large polyps or wart-like lesions in the nose, conjunctiva and occ
asionally in ears, larynx, bronchus, penile urethra, vagina, rectum and skin. The
causative fungus is Rhinosporidium seeberi
 Systemic Fungi
• Dimorphic fungal pathogens - exist in a mold form in nature or in the laboratory at dormant stage, only to
reactivate when the individual becomes immunosuppressed and is living in an area where the fungus is
not endemic.
• Mold at 25° C to 30° C and in a yeast or spherule form in tissues or when grown on enriched medium in the
laboratory at 37° C
• Known as endemic pathogens
• organisms in this group are considered primary systemic pathogens because of their ability to cause
infection in both “normal” and immunocompromised hosts and for their tendency to involve the deep
viscera after dissemination of the fungus from the lungs after its inhalation from nature
• also known as endemic pathogens, in that their natural habitat is delimited to specific geographic regions
and infection caused by a particular fungus is acquired by inhalation of spores from that specific
environment and geographic location
• H. capsulatum, C .immitis (C. posadasii), and P. marneffei have emerged as major opportunistic pathogens
in individuals with acquired immunodeficiency syndrome (AIDS) and other forms of immunosuppression.
Recognition of these endemic mycoses may be complicated by the fact that they may become manifest
only after the patient has left the area of endemicity. Often the infection may be quiescent, only to
reactivate when the individual becomes
• immunosuppressed and is living in an area where the fungus is not endemic
Dimorphic pathogens include:
Systemic Fungi
• Blastomyces dermatitidis,
• Coccidioides immitis and Coccidioides posadasii,
• Histoplasma capsulatum var. capsulatum and H. capsulatum var duboisii,
• Paracoccidioides brasiliensis,
• Penicillium marneffei
• is not transmitted from patient to patient; however, laboratory-acquired primary cutaneous and pulmonary
blastomycosis has been reported.
• 1. Blastomycosis - Chronic infection of the lungs which may spread to other tissues, particularly skin, bone
and genitourinary tract
• Caused by Blastomyces dermatitidis
• Soil is considered to be the source of infection and in decomposing matter such as wood and leaves - by
inhalation
• North American Blastomycosis - endemic and most cases occur in the United States and Canada
• confined to specific geographic regions, with most infections originating in the Mississipp River basin, around
the Great Lakes, and in the southeastern region of the United States (see Figure 72-2). Cases have also been
diagnosed in other parts of the world, including Africa, Europe, and the Middle East.
1. Asymptomatic Pathogenesis
2. Chronic pneumonia
3. Disseminated diseases: form multiple abscesses in various parts of the body.
4. Cutaneous blastomycosis: usually on the skin of the face or other exposed
parts of the body.
Symptoms usually appear between 3 weeks and 3 months after a person
breathes in the fungal spores

• People can get blastomycosis after breathing in the microscopic fungal spores
from the air. Although most people who breathe in the spores don’t get sick,
some of those who do may have flu-like symptoms, and the infection can
sometimes become serious if it is not treated..
• Outbreaks of infection have been associated with occupational or recreational
contact with soil, and infected individuals include all
• ages and both genders.
 Pathogenesis
• In the lungs - spores convert into large (15 to 20mm) invasive yeasts- form characteristic
broad-based buds.
 infection may remain localized in the lungs
• Hematogenous dissemination - cause focal infection in numerous organs, including the skin,
prostate, epididymides, testes, kidneys, vertebrae, ends of long bones, subcutaneous tissues,
brain, oral or nasal mucosa, thyroid, lymph nodes, and bone marrow
• Extrapulmonary disseminated blastomycosis, symptoms depend on the organ involved
• As with most of the endemic mycoses, the severity of symptoms and course of the disease is
dependent on the extent of exposure and the immune status of the exposed individual. Based
largely on studies of blastomycosis outbreaks, it appears that symptomatic disease occurs in
less than half of infected individuals.
• Pulmonary blastomycosis may be asymptomatic or present as a mild flulike illness. More
severe infection resembles bacterial pneumonia with acute onset, high
• fever, lobar infiltrates, and cough.
• A more subacute or chronic respiratory form of blastomycosis may resemble tuberculosis or
lung cancer, with radiographic presentation of pulmonary mass lesions or fibronodular
infiltrates.
 Pathogenesis
• Skin lesions - most common site of dissemination; they may be single or multiple and
may occur with or without clinically apparent pulmonary involvement
• Papules or papulopustules - on exposed surfaces and spread slowly.
 Painless abscesses, - pinpoint to 1 mm in diameter - develop on the advancing
borders.
 Irregular, wartlike papillae may form on surfaces.
 As lesions enlarge, the centers heal, forming atrophic scars.
 When fully developed, an individual lesion appears as an elevated verrucous patch,
usually ≥ 2 cm wide with an abruptly sloping, purplish red, abscess-studded border.
• Ulceration may occur if bacterial superinfection is present.
• cutaneous form of blastomycosis is almost always the result of hematogenous
dissemination from the lung, in most instances without evident pulmonary lesions or
systemic symptoms. The lesions may be papular, pustular, ulcerative nodular, with
crusted surfaces and raised borders. They are usually painless and are localized to
exposed areas, such as the face, scalp, neck, and hands. They may be mistaken for
squamous cell carcinoma.
• If bone lesions develop, overlying areas are sometimes swollen, warm, and
tender.
• Genital lesions cause painful epididymal swelling, deep perineal discomfort,
or prostatic tenderness detected during rectal examination.
• Central nervous system involvement can manifest as brain abscess, epidural
abscess, or meningitis.
Blastomycosis is relatively uncommon among individuals with AIDS or other
immunocompromising conditions.
However, when it occurs in these individuals, it tends to be acute, involve the
CNS, and have a much poorer prognosis.
 Treatment
• Untreated blastomycosis is usually slowly progressive and is rarely
ultimately fatal.
• Treatment of blastomycosis depends on severity of the infection.
 For mild to moderate disease, itraconazole
 For severe, life-threatening infection, amphotericin B
• The decision to treat patients with blastomycosis must take into
consideration the clinical form and severity of
• disease, as well as the immune status of the patient and the toxicity of
antifungal agents. Clearly, pulmonary blastomycosis
• in immunocompromised patients and those with progressive pulmonary
disease should be treated.
 2. Paracoccidioidomycosis

• chronic granulomatous disease of the skin, mucosa,

lymph nodes and internal organs.
• Called ‘South American blastomycosis’.
• Caused by Paracoccidioides brasiliensis
• Specific habitat not exactly known, but it has been
found in soil near armadillo burrows.
 Pathogenesis
• primary pulmonary infection that spreads by hematogenous route to mucosa of the nose, mouth
and the gastrointestinal tract, skin, lymphatic system, and the internal organs - producing chronic
granulomatous reaction
• Most often affects men who work outdoors in rural areas
• Symptoms can be different for different groups of people
• In adults - usually affects the lungs and causes lesions in the mouth and throat
• Children- are more likely to have swollen lymph nodes and skin lesions.
• Paracoccidioidomycosis can occur in healthy people and people with weakened immune systems.
In people with weakened immune systems (for example, due to HIV/AIDS), the symptoms usually
get worse more quickly.
• It’s difficult to avoid breathing in the fungus that causes paracoccidioidomycosis in areas where it’s
common in the environment. Many people who breathe in this fungus never get sick from it.
• hematogenous route - adjective. originating in the blood. producing blood or components of
blood. distributed or spread by way of the bloodstream, as in metastases of tumors or in
infections; blood-borne.
 Treatment
• Can be treated with antifungal medicines such as
itraconazole and amphotericin B.
• Another medicine often used is
trimethoprim/sulfamethoxazole (TMP/SMX), also known
as co-trimoxazole and by several different brand names,
including Bactrim, Septra, and Cotrim.
• Patients usually need treatment for about one year.
 3. Coccidioidomycosis
• Primarily an infection of the lungs caused by Coccidioides immitis ( also and C.
posadasii),
• C. immitis is localized to California, and C. posadasii accounts for the majority of
infections outside of California.
• Fungus was also recently found in South-central Washington.

• Coccidioidomycosis is an endemic mycosis caused by either of two indistinguishable

species, Coccidioides immitis and C. posadasii. The disease is caused by the inhalation of
infectious arthroconidia (Figure 72-6) and may range from asymptomatic infection (in
most people) to progressive infection and death. The two species differ in geographic
distribution
1. Asymptomatic Clinical Features
2. Primary pulmonary disease: condition is called valley fever, San Joaquin
Valley fever or desert rheumatism
3. Disseminated disease: Chronic progressive disseminated disease (coccidioidal
granuloma) which is highly fatal.
 been called “the great imitator.”
• as been called “the great imitator.” Synonyms for coccidioidomycosis include
coccidioidal granuloma and San Joaquin Valley fever among others. People can
get Valley fever by breathing in the microscopic fungal spores from the air,
although most people who breathe in the spores don’t get sick. Usually, people
who get sick with Valley fever will get better on their own within weeks to
months, but some people will need antifungal medication.

• Certain groups of people are at higher risk for becoming severely ill. It’s difficult
to prevent exposure to Coccidioides in areas where it’s common in the
environment, but people who are at higher risk for severe Valley fever should try
to avoid breathing in large amounts of dust if they’re in these areas.
• Risk factors for disseminated Coccidioidomycosis
Risk factor Highest risk

Age Infants and elderly

Sex Male

Genetics Filipino>African american> Native

american>Hispanic>Asian

Serum CF antibody titer >1:32

Pregnancy Late pregnancy and postpartum

Skin test Negative

Depressed cell-mediated immunity Malignancy, Chemotherapy, steroid

treatment, HIV infection
 Treatment
• Concurrent risk factors (organ transplant, HIV infection, high doses of corticosteroids) or when there is
evidence of unusually severe infection treatment is necessary.
• 3rd trimester of pregnancy or during the immediate postpartum period requires treatment with
amphotericin B.
• Immunocompromised patients or others with diffuse pneumonia should be treated with amphotericin B
followed by an azole (either fluconazole, itraconazole, posaconazole, or voriconazole) as maintenance
therapy.
• Total length of therapy should be at least 1 year.
• Immunocompromised patients should be maintained on an oral azole as secondary prophylaxis.
• Most individuals with primary coccidioidomycosis do not require specific antifungal therapy. For those with
concurrent risk factors (see Table 72-3), such as organ
• transplant, HIV infection, high doses of corticosteroids, or when there is evidence of unusually severe
infection, treatment is necessary. Primary occidioidomycosis in the third trimester of pregnancy or during
the immediate postpartum period requires treatment with amphotericin B.
• Immunocompromised patients or others with diffuse pneumonia should be treated with amphotericin B
followed by an azole (either fluconazole, itraconazole,
• posaconazole, or voriconazole) as maintenance therapy. The total length of therapy should be at least 1
year. Immunocompromised patients should be maintained on an oral azole as secondary prophylaxis.
 4. Histoplasmosis
• An intracellular infection of the reticuloendothelial system caused by Histoplasma
capsulatum
• Acquired by inhalation
• Most infections are asymptomatic.
• Some infected persons develop pulmonary disease which resembles tuberculosis.
• has a worldwide distribution but is most common in the USA.
• 25 authentic cases of histoplasmosis have been reported from India.
• H. capsulatum var. capsulatum, grows in soil with a high nitrogen content, especially in
areas contaminated with the excreta of bats and birds.
 A. Pulmonary Infection

• Chronic form of histoplasmosis occurs mainly in adults

• Closely resembles tuberculosis
• Caused by two varieties of Histoplasma capsulatum: H.
capsulatum var. capsulatum and H. capsulatum var. duboisii
• usual route of infection for both varieties of histoplasmosis is
via inhalation of microconidia, which in turn germinate into
yeasts within the lung and may remain
• localized or disseminate hematogenously or by the lymphatic
system
 A. Pulmonary Infection
• H. capsulatum var. capsulatum causes pulmonary and disseminated infections in
the eastern half of the United States and most of Latin America
• H. capsulatum var. duboisii causes predominately skin and bone lesions and is
restricted to the tropical areas of Africa
• Outbreaks of histoplasmosis have been associated with exposure to bird roosts,
caves, and decaying buildings or urban renewal projects involving excavation and
demolition.
• The clinical presentation of histoplasmosis caused by H. capsulatum var. capsulatum
is dependent upon the intensity of exposure and immunologic status of the host.
Asymptomatic infection occurs in 90% of individuals after a low-intensity exposure.
In the event of an exposure to a heavy inoculum, however, most individuals exhibit
some symptoms.
 A. Pulmonary Infection
• Self-limited form is marked by a flulike illness with fever,
chills, headache, cough, myalgias, and chest pain
• Acute infections resolve with supportive care and do not
require specific antifungal treatment
• Rare complication known as mediastinal fibrosis, in which
persistent host response to the organism may result in
massive fibrosis and constriction of mediastinal structures,
including the heart and great vessels.
 B. Disseminated Histoplasmosis
• Disseminated infection occurs most often in old age and infancy, or in
individuals with impaired immune responses.
• The reticuloendothelial system is involved with resultant
lymphadenopathy, hepatosplenomegaly, fever, anemia and a high rate of
fatality.
• Disseminated histoplasmosis follows acute infection in 1 in 2000 adults
and is much higher in children and immunocompromised adults.
Disseminated disease may assume a chronic, subacute, or acute course.
Chronic disseminated histoplasmosis is characterized by weight loss and
fatigue, with or without fever. Oral ulcers and hepatosplenomegaly are
common.
 C. Skin and Mucosa
• Granulomatous and ulcerative lesions may
develop on the skin and mucosa.
Treatment
• Amphotericin B is the treatment of choice for
most forms of disseminated histoplasmosis;
this is followed by oral itraconazole in
immunocompromised patients.
 African Histoplasmosis

• Caused by H. Capsulatum val. duboisii.

– morphologically identical to H. Capsulatum in its mycelial phase but differs in the
yeast phase both in vivo and in vitro and but the yeast phase has larger cells (12–15
μm diameter).
• mainly restricted to the continent of Africa.
• involves mainly the skin, subcutaneous tissues and bones.
• The lungs are not commonly affected and the disseminated disease is infrequent.
• In contrast to classic histoplasmosis, pulmonary lesions are uncommon in African
histoplasmosis. The localized form of histoplasmosis duboisii is a chronic disease
characterized by regional lymphadenopathy, with lesions of skin and bone.
 Key Points
• Blastomycosis: Blastomycosis is caused by Blastomyces dermatitidis
• It is also known as North American blastomycosis.
• Coccidioidomycosis is primarily an infection of the lungs caused by Coccidioides
immitis
• Infection is acquired by inhalation of dust containing arthrospores of the fungus.
• Histoplasmosis: primarily a disease of reticuloendothelial system caused by an
intracellular fungus Histoplasma capsulatum, a dimorphic fungus.
• H. capsulatum causes acute pulmonary histoplasmosis, chronic pulmonary
histoplasmosis, and progressive disseminated histoplasmosis
 Mycotoxicosis
presenting symptoms and severity depend on:

1.Type of mycotoxin;
2.Amount and duration of exposure;
3.Route of exposure;
4.Age, sex and health of the exposed individual.
5.Other circumstances, such as malnutrition, alcohol abuse,
infectious disease status, and other toxin exposures,may act
synergistically to compound
 Introduction
• More than 100 toxigenic fungi and more than 300 compounds now
recognized as mycotoxins
• Number of people affected is unknown
• Majority result from eating contaminated foods.
• Some mycotoxins are dermonecrotic, and cutaneous or mucosal contact with
mold-infected substrates may result in disease
• Inhalation of spore-borne toxins also constitutes an important form of
exposure.
• Supportive therapy, there are almost no treatments for mycotoxin exposure.
• Not communicable from person o person.
 Mycetis M
 Or mycetismus
Fungus which is eaten causes toxic
effects
Mushroom poisoning
May cause gastrointestinal disease,
dermatitis or death. Amanita phalloides accounts for the majority of
fatal mushroom poisonings worldwide.
 Mycotoxicosis
Result from ingestion of food or feed that contains mycotoxins.
Variety of mycotoxins are produced by mushrooms (e.g. Amanita
species), and their ingestion results in a dose-related disease
called mycetismus.
 Aflatoxin

Most potent, which is peptide elaborated by produced primarily

by Aspergillus flavus and Aspergillus parasiticus- other species of
aspergillus produce aflatoxins as well
Is a frequent contaminant of peanuts, corn, grains and other
foods.
Acute aflatoxicosis has been manifested in humans as an acute
hepatitis.
 Aflatoxin
Highly toxic to animals and birds, and
probably to human beings as well cause
hepatomas in ducklings and rats, and its
possible carcinogenic effect in human
beings has caused great concern.
Aflatoxin B1 is the most potent natural
carcinogen known and is the major
aflatoxin produced by toxigenic strains
 ergot Alkaloids
 Ergotoxicosis (ergotism) - toxic alkaloids produced by the
fungus claviceps purpurea - growing on the fruiting heads
of rye.
Lysergic acid - structure common to all ergot alkaloids
 Hallucinogen lysergic acid diethylamide (LSD) was
discovered as a result of research with these
compounds.
 ergot Alkaloids
Hardened masses of fungal
tissue (sclerotia) that are
formed when the fungus
invades the floret and
replaces the grain of wheat,
barley, or rye.
 other Mycotoxicoses

 Classic examples of human diseases caused by Fusarium

mycotoxins include alimentary toxic aleukia, Urov or Kashin–Beck
disease and Akakabibye (scabby grain intoxication).
Two of these are yellow rice toxicosis in Japan and alimentary toxic
aleukia in the former Soviet Union.
There are also other fungi responsible for mycotoxicosis .
 PsychotroPic Agents
 Toxic metabolites produced by
fungi have been used by
primitive tribes for religious,
magical and social purposes.
The hallucinogenic agents (d-
lysergic acid, psilocybin) are
produced by the Psilocybe
species and other fungi.
 PsychotroPic Agents
In the 20th century, problems
involving toxins of fungi were seen
with the recreational use of
psychotropic agents such as
psilocybin and psilocin, as well as
the semisynthetic derivative
lysergic acid diethylamide (LSD).
 Key Points
 Mycotic poisoning is of two types:
1. Mycetism
2. Mycotoxicosis
Aflatoxin is elaborated by Aspergillus flavus and related molds
Ergot alkaloids: Ergotoxicosis (ergotism) is due to the toxic
alkaloids produced by the fungus Clavice purpurea
 Key Points

 Psychotropic agents: Toxic metabolites produced by

fungi such as psilocybin and psilocin, as well as the
semisynthetic derivative lysergic acid diethylamide (LSD)
ANTIFUNGAL DRUGS
 A. Polyene Antifungals
General Characteristics
Polyenes bind to ergosterol in fungal membranes - creating ion channels -
leading to leakage and cell death.
Polyene membrane damage through an oxidative stress - rapid killing.
Polyenes also bind to cholesterol (but less avidly than ergosterol - are quite
toxic.
 Toxicity is reduced by the use of liposomal formulations.
Have poor gastrointestinal absorption.
 Amphotericin B (AMB)
 administered intravenously (IV) for serious fungal
infections and has been the drug of choice for most
life-threatening fungal infections.
 Resistance is infrequent, - there is some reduced
AMB sensitivity among some Candida species.
 Resistance is associated with lower membrane levels
of ergosterol.
 Liposomal AMB formulations are available that
have reduced toxicity.
 used in combinations with 5-fluorocytosine or
fluconazole but only with very specific fungi in
specific body locales.
 Amphotericin B (AMB)
MB also stimulates the fungus to produce
oxygen radicals, and to modulate macrophage
activity by stimulating production of pro-
inflammatory cytokines, reactive oxygen
intermediates and nitric oxide
the small size of these liposomes (<100 nm)
results in prolonged circulation allowing
distribution into many different organs
ensures that AMB remains associated with the
liposome bilayer until it comes into contact
with a fungus, minimizing the adverse effects of
AMB on host tissues
 Nystatin
not absorbed from the gastrointestinal tract
used topically, intravaginally, or orally to treat Candida
overgrowth or infections of cutaneous or mucosal
surfaces.
B. 5-Fluorocytosine (5-FC, flucytosine)
an antimetabolite converted in fungal cells to 5-fluorouradylic
acid - competes with uracil to cause miscoding and disruption
of RNA, protein, and DNA synthesis.
resistance develops quickly if used alone - 5-FC is used in
combination with amphotericin B or fluconazole for specific
infections.
 C. Imidazole Drugs
Imidazole
azole drugs with two nitrogen in the
azole ring - commonly used for localized
surface infection
Inhibit the lanosterol 14-a-demethylase
interfering with ergosterol synthesis.
1. Ketoconazole - orally administered
but is used only in non–life-
threatening fungal infections.
2. Miconazole - used topically against
dermatophytes and candida spp.
 D. Triazoles
Azole Drugs
Triazole agents - have a broad spectrum of activity.
The most commonly used azoles, include fluconazole,
itraconazole, econazole, terconazole, butoconazole, and
tioconazole.
Newer triazoles (ie, voriconazole, posaconazole, ravuconazole)
are active against fluconazole-resistant strains of Candida.
 Fluconazole
 azole drugs with three nitrogen in the azole ring.
 better systemic activity than the Imidazoles.
1. Fluconazole
a) excellent oral bioavailability.
b) used for systemic infections - most commonly with Candida and
Coccidioides - Coccidioidal meningitis in acquired immunodeficiency
syndrome (AIDS), and as maintenance therapy after cryptococcal
meningitis.
c) used in combination with other drugs in specific situations for
specific fungi.
d) the proportion of a drug or other substance which enters the
circulation when introduced into the body and so is able to have an
active effect.
 Itraconazole
Lipophilic imidazole drug - administered orally.
Treatment of mucocutaneous candida infections, non–life-
threatening aspergillus infections, moderate or severe
histoplasmosis or blastomycosis, and sporotrichosis.
 Voriconazole
Has a broad spectrum of activity - exception of the non-septate
fungi (Zygomycetes)
may be effective against other fungi that have developed AMB
resistance.
Now a primary drug for treatment of invasive aspergillosis as an
alternative to AMB
 Posaconazole
a newer azole licensed for treatment of Zygomycetes (non-
septate fungi) infections.
Echinocandins
Inhibit fungal glucan synthesis - leading to a weakened cell
wall and cell lysis.
1. Include caspofungin, micafungin, and anidulafungin.
2. Effective against Aspergillus spp., Candida spp.,
Pneumocystis jiroveci, and a variety of other fungi.
 Topical Antifungal
including Imidazoles, Allylamines - terbinafine and naftifine,
tolnaftate, and many others
may be used for dermatophytes and mucosal yeast
infections.