The Fungi of Medical

Importance
Department of Microbiology and Parasitology
  Introduction
 Fungi as Infectious Agents
 Organization of Fungal Disease
 Subcutaneous Mycoses
Topics  Cutaneous Mycoses
 Superficial Mycoses
 Opportunistic Mycoses
 Fungal Allergies and Intoxication
  The term "mycology" is derived from Greek word "mykes"
meaning mushroom.
 Therefore mycology is the study of fungi.
 The ability of fungi to invade plant and animal tissue was first
documented in animal infection by any fungus was made by Bassi
Terms and in 1835

History  Bassi studied the muscardine disease of silkworm and proved the
that the infection was caused by a fungus Beauveria bassiana.
 In 1910 Raymond Sabouraud published his book Les Teignes, which
was a comprehensive study of dermatophytic fungi.
 Raymond Sabouraud is also regarded as father of medical
mycology.
  Fungi inhabit almost every niche in the environment
Importance of
 Humans and animals are exposed to these organisms in
Fungi various fields of life.
 1.They are eukaryotic
a. Cells contain membrane bound cell organelles including nuclei,
mitochondria, golgi.apparatus, endoplasmic reticulum, lysosomes
etc.
b. Exhibit mitosis.

General 2.Have ergosterols in their membranes and possesses 80S

ribosomes.
Properties of 3.Have a rigid cell wall and are therefore non-motile, a feature that
Fungi separates them from animals.
a. All fungi possess cell wall made of chitin.

4.Are chemoheterotrophs (require organic compounds for both

carbon and energy sources)
a. Fungi lack chlorophyll
b. Therefore not autotrophic.
 5.Fungi are osmiotrophic; they obtain their nutrients by absorption.
6.They obtain nutrients as saprophytes (live off of decaying matter)
or as parasites (live off of living matter).
General 7.All fungi require water and oxygen and there are no obligate
Properties of anaerobes.
8.Typically reproduce asexually and/or sexually by producing spores.
Fungi (2) 9.They grow either reproductively by budding or non-reproductively
by hyphal tip elongation.
10.Food storage is generally in the form of lipids and glycogen.
Asexual Spores
Formation
Types of
Spores
Fungi vs
Bacteria
  Fungi were initially classified with plants and were a subject of
interest for botanists.
 In 1969 R.H Whittaker classified all living organisms into five
kingdoms namely Monera, Protista, Fungi, Plantae and Animalia.
Classification  Traditionally the classification proceeds in this fashion:
 Kingdom - Subkingdom - Phyla/phylum - Subphyla - Class - Order -
of Fungi Family - Genus- Species
 This classification is too complicated to be dealt here.

 More practical approaches, one based on sexual reproduction and

the other based on morphology of the thallus (vegetative
structure).
 1. Zygomycetes: which produce through production of
zygospores.
Classification 2. Ascomycetes: which produce endogenous spores called
Based on ascospores in cells called asci.

Sexual 3. Basidiomycetes: which produce exogenous spores called

basidiospores in cells called basidia.
Reproduction 4. Deuteromycetes (Fungi imperfecti): fungi that are not known to
produce any sexual spores (ascospores or basidiospores).
Sexual Cycle in
Basidio
mycetes
Sexual Cycle in
Zygomycetes
  Moulds (Molds): Filamentous fungi
 Eg: Aspergillus sps, Trichophyton rubrum

 Yeasts: Single celled cells that buds

 Eg: Cryptococcus neoformans, Saccharomyces cerviciae
Classification  Yeast like: Similar to yeasts but produce pseudohyphae Eg:
Candida albicans
Based on
 Dimorphic: Fungi existing in two different morphological forms at
Morphology two different environmental conditions.
 They exist as yeasts in tissue and in vitro at 37 0C and as moulds in
their natural habitat and in vitro at room temperature.
 Eg: Histoplasma capsulatum, Blastomyces dermatidis,
Paracoccidiodes brasiliensis, Coccidioides immitis, Pennicilium
marnefei
  Yeast cells reproducing by
nuclear fission and
blastoconidia formation.
Fungal cell
 The elongation of budding
morphology yeast cells to form
pseudohyphae is shown, as is
the formation of a germ tube
SUNARYATI SUDIGDOADI 20
 1. Distinguish between the characteristics indicative of true versus
opportunistic fungal pathogens.
Fungi as
2. Relate opportunistic fungal infections to those conditions that
Infectious predispose patients to infection.
Agents 3. Explain the geographical limits associated with fungal
pathogens.
4. List the most important antifungal defenses found in humans.
The Objectives 5. Understand why direct examination of patient samples is often
part of the diagnostic process.
 A. Microscopic fungi (molds
and yeasts) are
widespread in nature. A
few members cause fungal
Fungi as diseases or mycoses.

Infectious B. Infectious fungi occur in

groups based upon the
Agents virulence of the pathogen
and the level of
involvement, whether
systemic, subcutaneous,
cutaneous, or superficial.
Representative
Fungal
Pathogen,
Degree of
Pathogenicity,
and Habitat
Fungal
Pathogens:
System Profile
  Most fungal pathogens do not require a host to complete their life
cycles and infections are not communicable.
 Dermaphytes and Candida sp naturally inhabit human body and
are transmissible.
Epidemiology  True fungal pathogens are distributed in a predictable
of the Mycoses geographical pattern - climate, soil.
 Dermaphytoses most prevalent
 Cases go undiagnosed or misdiagnosed.
 Systemic, subcutaneous, cutaneous or superficial infections

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Distribution of
the Four True
Fungal
Pathogens
 C. True or primary pathogens have virulence factors that allow
them to invade and grow in a healthy host.
1. They are also thermally dimorphic, occurring as hyphae in their
natural habitat and converting to yeasts while growing as
parasites at body temperature (378C).
2. Inhaled spores initiate primary pulmonary infection (PPI), which
Fungi as 3.
can spread to the skin and other systems.
Diseases are not transmissible and cause a long-term allergic
Infectious reaction to fungal proteins.
4. True pathogens are endemic to certain geographic areas.
Agents (2)
D. Opportunistic fungal pathogens are normal flora or common
inhabitants of the environment that invade mainly patients
whose host defenses are compromised.
1. They are only weakly virulent and lack thermal dimorphism.
2. Infections may be local, cutaneous, or systemic and are currently
on the rise, due to more weakened patients.
Primary and
Opportunistic
Fungal
Pathogens
Comparison of
True and
Opportunistic
Fungal
Infections
Predisposing
Factors
  Opportunistic fungal pathogen has little or no virulence; host
defenses must be impaired.
Emerging  Vary from superficial and colonization to potentially fatal systemic
disease
Fungal  An emerging medical concern; account for 10% of all nosocomial
Pathogens infections
 Dermatophytes may be undergoing transformation into true
pathogens.

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  Portal of entry
 Primary mycoses – respiratory portal; inhaled spores
 Subcutaneous - inoculated skin; trauma
Pathogenesis  Cutaneous and superficial – contamination of skin surface
of the Fungi  Virulence factors – thermal dimorphism, toxin production,
capsules and adhesion factors, hydrolytic enzymes, inflammatory
stimulants

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The General
Changes
Associated
with Thermal
Dimorphism
 E. Immunity to fungal infections consists primarily of nonspecific
barriers, inflammation, and cell-mediated defenses.
 Antibodies and antigens may be used to detect disease in some
cases.

Fungi as F. Diagnosis and identification require

1. Microscopic examination of stained specimens,
Infectious 2. Culturing of pathogen in selective and enriched media, and
Agents (3) 3.
4.
Specific biochemical and in vitro serological tests.
Skin testing for true and opportunistic pathogens can determine
prior disease but is not useful in diagnosis.

G. Control of fungal infections involves drugs such as intravenous

amphotericin B, flucytosine, azoles (fluconazole), and nystatin.
Methods of
Processing
Specimens
and
Identifying
Fungal
Isolates
 blunt scalpel

bone curette
Antifungal
Drugs
 1. Summarize the aspects of systemic mycotic infection common
to all fungal pathogens.
2. Recall the habitat, geographic distribution, and diseases
Organization associated with Histoplasma capsulatum, Coccidioides immitis,
of Fungal Blastomyces dermatitidis, and Paracoccidioides brasiliensis.
3. Summarize the pathology of each of the four fungal pathogens.
Diseases 4. Understand the means by which infection with Histoplasma
capsulatum, Coccidioides immitis, Blastomyces dermatitidis, and
Paracoccidioides brasiliensis is diagnosed in the laboratory.
  They are restricted to certain endemic regions of the world.
 Infection occurs when soil or other matter containing the fungal
conidia is disturbed and the spores are inhaled into the lower
respiratory tract.
Systemic  The spores germinate in the lungs into yeasts or yeastlike cells and
produce an asymptomatic or mild primary pulmonary infection
Infections by (PPI) that parallels tuberculosis.
True  In a small number of hosts, this infection becomes systemic and
creates severe, chronic lesions.
Pathogens
 In a few cases, spores are inoculated into the skin, where they
form localized granulomatous lesions.
 All diseases result in immunity that can be long term and that
manifests clinically as an allergic reaction to fungal antigens.
 A. Histoplasmosis (Ohio Valley fever)
Systemic B. Coccidioidomycosis (valley fever)
Infections by C. Blastomycosis (Chicago disease)
True D. Paracoccidioidomycosis (South American
Pathogens blastomycosis)
  Darling’s disease, Ohio Valley fever, and reticuloendotheliosis.
 Histoplasma capsulatum – most common true pathogen; causes
histoplasmosis
 Typically dimorphic, growth on media below 35 0C is characterized
Histoplasmosis by a white or brown, hairlike mycelium; and growth at 37 0C
produces a creamy white, textured colony.
Ohio Valley  Identified by Tiny intracellular yeasts in macrophages or free
Fever yeasts in samples of sputum or cerebrospinal fl uid.
 Inhaled conidia produce primary pulmonary infection that may
progress to systemic involvement of a variety of organs and
chronic lung disease.
 Grows in moist soil high in nitrogen content
 Amphotericin B, ketoconazole
Histoplasmosis
Ohio Valley
Fever
  Coccidioides immitis - causes coccidioidomycosis
 Distinctive morphology – blocklike arthroconidia in the free-living
stage and spherules containing endospores in the lungs
 Identified by appearance of spherules in the sputum, spinal fluid,
and biopsies. Identification is enhanced by the cultivation of
Coccidioido mycelia growth and induction of spherules. Immunodiffusion and
latex agglutination tests on serum samples aid in early diagnosis.
mycosis: Valley  Arthrospores inhaled from dust, creates spherules and nodules in
Fever the lungs
 Amphotericin B treatment

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Coccidioido
mycosis: Valley
Fever

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  Blastomyces dermatitidis- causes blastomycosis
 Dimorphic
 Identified by Smears displaying large, ovoid, thick-walled yeast
cells with oversize buds provide presumptive identification. ELISA
Blastomyces and complement fixation tests can verify infection.
dermatitidis:  Inhaled 10-100 conidia convert to yeasts and multiply in lungs
 Symptoms include cough and fever.
North  Chronic cutaneous, bone, and nervous system complications
American  Amphotericin B
Blastomycosis

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Blastomyces
dermatitidis:
North
American
Blastomycosis

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  Paracoccidioides brasiliensis
 Distributed in Central and
South America
 Lung infection occurs
Paracoccidioi through inhalation or
inoculation of spores.
domycosis
 Systemic disease is not
common.
 Ketoconazole, amphotericin
B, sulfa drugs

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  Describe the progression of a typical subcutaneous mycosis.
 Summarize the major characteristics of Sporothrix schenckii.
Subcutaneous  Recall the characteristics of chromoblastomycosis and
Mycoses phaeohyphomycosis.
 Describe the progression of events leading to mycetoma and
chromoblastomycosis, as well as the prognosis of each disease.
  Lymphocutaneous sporotrichosis
Subcutaneous  Chromoblastomycosis

Mycoses  Mycetoma

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  Sporotrichosis (rose-gardener’s
disease)
 Very common saprobic fungus
that decomposes plant matter in
soil
 Infects appendages and lungs
 Lymphocutaneous variety occurs
Sporothrix when contaminated plant matter
schenckii penetrates the skin and the
pathogen forms a nodule, then
spreads to nearby lymph nodes.

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  A progressive subcutaneous mycosis characterized by highly
visible verrucous lesions
Chromoblasto  Etiologic agents are soil saprobes with dark-pigmented mycelia
and spores
mycosis  Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporium carrionii
 Produce very large, thick, yeastlike bodies, sclerotic cells

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  When soil microbes are accidentally implanted into the skin
 Progressive, tumorlike disease of the hand or foot due to chronic
fungal infection; may lead to loss of body part
 Caused by Pseudallescheria or Madurella

Mycetoma

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Cutaneous
 Name the three dermatophytic genera and the diseases they
Mycoses cause.
and  Understand the pathology, epidemiology, and treatment of
ringworm
Superficial  Explain the significance of superficial mycoses.
Mycoses
  Infections strictly confined to keratinized epidermis (skin, hair,
nails) are called dermatophytoses- ringworm and tinea
 39 species in the genera Trichophyton, Microsporum,
Epidermophyton
 Closely related and morphologically similar
Cutaneous
 Causative agent of ring worm varies case to case
Mycoses

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Dermatophyte

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  Natural reservoirs- humans, animals, and soil
 Infection facilitated by moist, chafed skin
 Long infection period followed by localized inflammation and
allergic reactions to fungal proteins
 Ringworm of scalp (tinea capitis) affects scalp and hair-bearing
regions of head; hair may be lost.
Dermatophyte
 Ringworm of beard (tinea barbae) affects the chin and beard of
adult males; contracted mainly from animals.
 Ringworm of body (tinea corporis) occurs as inflamed, red ring
lesions anywhere on smooth skin.
 Ringworm of groin (tinea cruris) “jock itch” affects groin and
scrotal regions.

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Dermatophyte
  Ringworm of foot and hand (tinea pedis and tinea manuum) is
spread by exposure to public surfaces; occurs between digits and
on soles.
 Ringworm of nails (tinea unguium) is a persistent colonization of
the nails of the hands and feet that distorts the nail bed.
Dermatophyte  Treatment of dermatophytes includes topical antifungal agents –
tolnaftate, miconazole applied for several weeks.
 Lamisil or griseofulvin 1-2 years

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  Tinea versicolor – caused by
Malassezia furfur; elicits mild,
chronic scaling, mottling of
skin; also implicated in
folliculitis, psoriasis, and
seborrheic dermatitis
Superficial  White piedra – caused by
Trichosporon beigelii; whitish
Mycoses or colored masses develop
scalp, pubic, or axillary hair
 Black piedra – caused by
Piedraia hortae; dark-brown
to black gritty nodules,
mainly on scalp hairs

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Tinea
versicolor –
Malassezia
furfur
Opportunistic
 Name the most common opportunistic fungal pathogens.
Mycoses  Explain the epidemiology of candidiasis.
and  Relate the options available for treatment of common fungal
Fungal opportunists.
 Distinguish between fungal infections, fungal allergies, and fungal
Allergies and intoxications.
Intoxications
  Most important fungal
pathogens:
Aspergillus

Opportunistic Candida
Cryptococcus
Mycoses Pneumocystis
Rhizopus
Mucor
Absidia

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  Candida albicans
 Widespread yeast
 Infections can be short-lived,
superficial skin irritations to
Infections by overwhelming, fatal systemic
diseases.
Candida:
 Budding cells of varying size
Candidiasis that may form both elongate
pseudohyphae and true
hyphae
 Forms off-white, pasty
colony with a yeasty odor

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  Normal flora of oral cavity, genitalia, large intestine or skin of 20%
of humans
 Account for 80% of nosocomial fungal infections
 Account for 30% of deaths from nosocomial infections
Candida  Thrush – occurs as a thick, white, adherent growth on the mucous
membranes of mouth and throat
albicans  Vulvovaginal yeast infection – painful inflammatory condition of
the female genital region that causes ulceration and whitish
discharge
 Cutaneous candidiasis – occurs in chronically moist areas of skin
and in burn patients

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  Presumptive diagnosis made
if budding yeast cells and
pseudohyphae are found;
germ tube
 Growth on selective,
Diagnosis and differential media
differentiates Candida
Treatment species
 Topical antifungals for
superficial infections,
amphotericin B and
fluconazole for systemics

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  Cryptococcus neoformans
causes cryptococcosis.
 A widespread encapsulated
yeast that inhabits soil
Cryptococcus around pigeon roosts
 Common infection of AIDS,
neoformans cancer or diabetes patients
and  Infection of lungs leads to
cough, fever, and lung
Cryptococcosis nodules
 Dissemination to meninges
and brain can cause severe
neurological disturbance and
death.

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  Has a spherical to ovoid
shape, with small,
constricted buds and a large
capsule that is important in
its pathogenesis
 Negative stain
Diagnosis and demonstrating encapsulated
Treatment budding yeast
 Biochemical tests, serological
testing
 Systemic infection requires
amphotericin B and
fluconazole.

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  A small, unicellular fungus that
causes pneumonia (PCP), the most
prominent opportunistic infection
in AIDS patients
 This pneumonia forms secretions in
Pneumocystis the lungs that block breathing and
can be rapidly fatal if not controlled
(carinii) jiroveci with medication.
 DNA amplification probe can
and provide rapid confirmation of
infection.
Pneumocystis  Traditional serological tests for
antigens and antibodies are not
Pneumonia useful diagnostic tools for
Pneumocystis.
 Lacks ergosterol, has a weak cell
wall, and isan obligate parasite
 Pentamidine and cotrimoxazole

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  Very common airborne soil fungus
 600 species, 8 involved in human disease; A. fumigatus most
commonly
Aspergillosis:  Serious opportunistic threat to AIDS, leukemia, and transplant
Diseases of patients
 Infection usually occurs in lungs – spores germinate in lungs and
the Genus form fungal balls; can colonize sinuses, ear canals, eyelids, and
conjunctiva
Aspergillus  Invasive aspergillosis can produce necrotic pneumonia, and
infection of brain, heart, and other organs.
 Amphotericin B and nystatin

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Aspergillosis:
Diseases of the
Genus
Aspergillus
  Zygomycota are extremely
abundant saprobic fungi
found in soil, water, organic
debris, and food.
 Genera most often involved
are Rhizopus, Absidia, and
Mucor.
Zygomycosis
 Usually harmless air
contaminants invade the
membranes of the nose,
eyes, heart, and brain of
people with diabetes and
malnutrition, with severe
consequences.

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  Any fungus can be
implicated in infections when
immune defenses are
severely compromised.
 Geotrichum candidum –
geotrichosis; mold found in
soil, dairy products; primarily
involved in secondary lung
Miscellaneous infections
 Genus Penicillium is not usually
infectious, although one species,
P. marneffei, is a true pathogen
restricted to certain parts of the
world (Southeast Asia) and is
occasionally isolated from cancer
and AIDS patients.

Opportunists  Fusarium species – soil;

occasionally infects eyes,
toenails, burned skin
 Unusual opportunistic
infections have been
reported for other
commonplace fungi such as
Alternaria, Malassezia, and
Exserohilum.

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  Fungal spores are common sources of atopic allergies.
 Seasonal allergies and asthma
 farmer’s lung, teapicker’s lung, bark stripper’s disease
Fungal  Fungal toxins lead to mycotoxicoses usually caused by eating
poisonous or hallucinogenic mushrooms.
Allergies and  aflatoxin toxic and carcinogenic; grains, corn peanuts; lethal to poultry
Intoxications and livestock

 Stachybotrys chartarum – sick building syndrome; severe

hematologic and neurological damage

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