INTRODUCTION
MYCOLOGY
•the separation of the fungi from the bacteria is based on the fundamental difference in nuclear structure of eukaryotes and prokaryotes
•fungi = eukaryotes (mb bound nucleus, chromosomes, mitochondria...) vs. bacteria = prokaryotes
•fungi cell walls contain complex polysaccharides (chitin, chitosan, glucans, mannans)
•fungi cell wall stains = Periodic Acid Schiff (PAS), Gomori’s Methenamine Silver stain (GMS), Calcifluor stain (CF)
•fungi plasma mb contains sterols, principally ergosterol (site of action of antifungal drugs/drug resistence)
Growth
•Yeasts are unicellular fungi (reproduce by budding or fission)
•Molds are multicellular fungi (germination » germ tube which grows from the tip (apical extension) » side branching » hyphae (network of filaments) » mycelium or thallus
•Hyphae: Nonseptate (=coenocytic or multinucleated) OR Septate
Reproduction
•Sexual vs. Asexual (not exclusive, one species may reproduce in one way, the other, or both ways)
•Asexual (Vegetative (special propagules not required) vs. Asexual Reproduction with Propagules (Conidia or Spores)
Asexual Reproduction with Propagules:
A. Conidia: develop from fertile hyphae via the blastic process (portion of hyphae blows-out before being separated by a septum) OR the thallic process (conversion of an entire
segment of hypha into a conidium)
1. Arthroconidum (thallic conidia which break loose from each other @ maturity to initiate growth by germination)
2. Blastoconidum (blastic conidia; most yeasts reproduce in this fashion so yeast cell = blastoconidium; pseudohyphae are formed when blastoconidia do not separate @ maturity;
molds also produce blastoconidia)
3. Chlamydoconidium (thallic conidia; thick-walled for survival, not multiplication)
4. Macroconidium (some fungi produce conidia of 2 separate sizes = microconidia & macroconidia; note terms do not indicate anything about conidiogenesis)
B. Sporangiospore: produced by cytoplasmic cleavage within a structure called a sporangium; nonseptate hyphae for the most part in sporangiospore formers
Sexual Reproduction: (not known to play a role in pathogenesis)
Miscellaneous
• Dimorphism: Zoopathogenic fungi may grow differently in tissue vs. nature/culture; often dictated by temperature (thermally dimorphic)
•Opportunistic Fungus Diseases: (diabetes, lymphomas, broad spectrum antibiotic therapy, immunosuppressed (HIV/AIDS, corticosteroids, x-irradiation, cytotoxic drugs) - Coccidioides,
Candida, Cryptococcus, Aspergillus, Mucor, Rhizopus, Pneumocystis
Page 1
MYCOLOGY
DISEASE
DEFINITIONS
EPIDEMIOLOGY
CLINICAL
LAB DX
THERAPY
DERMATOMYCOSES (any infectious disease of skin caused by fungus)
Epidermophyton, Trichophyton, Microsporum (DERMATOPHYTOSES - ringworm)
Ringworm or Tinea
6 Common Species:
•M. canis
•M. gypsum
•T. mentagrophytes
•T. rubrum
•T. tousurans
•E. foccusum
•confined almost exclusively to
cutaneous layers of body (hair,
nails)
•humans & other animals
•dermatophytes use keratin in
metabolism » keratinophiles
Source: (worldwide)
•Anthropophilic species = humans only;
reduced conidiation
•Zoophilic species = mainly other animals,
but sometimes humans
•Geophilic species = found in soil
•Differentiate Genera by their large,
multiseptate, elongate macroconidia
(thallic conidia):
1. Microsporum - echinulate
(spiky), spindle-shaped, thickwalled, borne singly
2. Trichophyton - cylindrical,
smooth, thin-walled, borne singly
3. Epidermophyton - smooth, clubshaped, mod thick-walled, borne in
clusters of 2 or 3 (microconidia are
absent)
Transmission:
•direct contact w/lesions OR infected
materials (hair, etc.) on fomites (inanimate
objects)
•contagious (almost all other mycoses are
not)
•involve the non-viable keratinized
layers of skin
•Tinea capitis (scalp/hair)
•Tinea barbae (chronic; bearded area)
•Tinea corporis (glabrous / smooth
skin)
•Tinea cruris (“jock strap itch”; groin,
perineum, perianal)
•Tinea pedis (“athlete’s foot”; feet,
toe webs, soles)
•Tinea unguim (nails)
General:
•definitive dx depends on the demonstration of a
dermatophyte by:
1. direct mount (scraping, KOH to dissolve
keratin, branching hyphae w/arthroconidia is
diagnostic, false negatives but not false positives,
ectothrix or endothrix from tinea capitis/barbae)
2. Wood’s Light (some species of Microsporum
cause hairs to flouresce a greenish-yellow color
upon UV light (365 nm) exposure; only 10% of
tinea capitis in humans is diagnosable w/Wood’s
light
Prescription drugs:
•Griseofulvin concentrates in keratinized
skin » virtually eradicated
tinea capitis in children
•Ketoconazole systemically & topically
Nonprescription drugs:
•applied topically
•usually effective
•recurrences common
•ingredients = undecylenic
acid, tolnoftate,
miconazole
3. Culture (Sabouraud’s dextrose agar OR some
similar recipe of dextrose & peptone w/ agar; add
chloramphenical & cycloheximide for selectivity
YEAST INFECTIONS
Candida
Candidiasis (or
candidosis)
•acute or subacute superficial
disease of skin, nails, & mucous
mbs
•rarely, it involves other deep-seated
areas of the body
Source/Transmission:
•endogenous/opportunistic
•Candida species are commensals of the GI
tract, vagina, & oral mucosae
•very common & may occasionally be
contagious (sexual contact)
•opportunistic during: early
infancy/pregnancy, traumatic changes,
endocrine dystrophies (DM), malnutrition,
malignancy, anemia, changes induced by
antibacterial or immunosuppressive drugs, or
immunosuppressed pts
•involve the skin, nails, and mucous
mbs, or rarely disseminate to other
organs
Cutaneous lesions:
•resemble dermatophytoses
•involve area around the nail » clubshaped fingers
•affect moist areas (groin, between
fingers, etc.)
•most common cause of diaper rash
Mucous Membranes:
•thrush (AIDS pts.)
•perleche (corners of mouth)
•vulvovaginitis
•Chronic mucocutaneous
candidiasis (CMC) affects
individuals w/ deficient CMI;
recurrent, but does not spread to deep
tissues
Systemic Disseminated Disease:
•neutropenia predisposes
•advanced malignancies (bladder or
bowel cancer)
•Hodgkin’s Disease
•BM Transplant
PULMONARY MYCOSES
Cryptococcus neoformans
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Appearance in Tissue & Exudates:
•yeast cells (blastoconidia) & hyphal elements
•hyphae normally pseudohyphae, but may be true
hyphae w/ C. albicans
•C. glabrata does not form hyphae
•C. ggilliermondii forms pseudohyphae sparingly
Appearance in Cultures:
•soft, cream-colored colonies
•often form pseudohyphae
•C. albicans can form germ tubes when incubated
@ 37°C in serum, etc. » true mycelium (but
short-lived)
ID of Candida in Lab:
1. Germ Tube Test: rapid ID of C. albicans
2. Formation of Pseudohyphae: most Candida
species (except C. glabrata) form pseudohyphae
when grown on Corn Meal Agar (CMA) w/
Tween-80; Chlamydoconidia (neither a conidium
or a spore) are formed on CMA by C. albicans
3. Substrate Assimilation: species ID on basis
of morphology on CMA & carbon source
assimilation products
•Fluconazole for
oropharyngeal or
esophageal thrush
•Clotrimazole or nystatin
for skin infections (topical)
•Ketoconazole for
mucocutaneous candidiasis
•Amphotericin B, w/ or
without flucytosine, or
ketoconazole for
disseminated candidiasis
•Reduce predisposing
factors
•Thrush may be prevented
by oral clotrimazole
troches OR nystatin
“swish & swallow”
MYCOLOGY
DISEASE
Cryptococcosis
“yeast meningitis” or
Cryptococcal
meningitis
DEFINITIONS
EPIDEMIOLOGY
CLINICAL
•chronic, wasting, frequently
fatal disease (untreated/
immunosuppressed)
characterized by a pronounced
predilection for the central
nervous system
•most often in immunocompromised hosts (but
Fluconazole has drastically
decreased the incidence)
•caused by a single species that
has both an anamorphic &
teleomorphic form of growth
•anamorphic form is an
encapsulated yeast w/ 2
biotypes, each of which has 2
serotypes (discerned based on
antigenic epitopes within the
capsule)
Source: (worldwide)
•2 biotypes of diff. geographic
distribution & diff. ecological
associations:
1. C. neoformans var. neoformans
(serotypes A & D): avian habitats,
esp. pigeons
2. C. neoformans var. gatii (serotypes
B & C): tropical & subtropical;
Eucalyptus trees
•Transmission: inhalation of
infectious conidia from an
exogenous source
•pulmonary cryptococcosis is
usually subclinical, but may
disseminate » meninges & brain
parenchyma (common sites)
•Skin lesions in 20% of
disseminated cases
LAB DX
THERAPY
Appearance in Tissue:
•blastoconidium w/capsule
•India ink stains the capsule for
visualization
•Amphotericin B +
Flucytosine for
meningitis or other
disseminated disease
Appearance in Culture:
•mucoid colonies that contain
encapsulated yeast cells (India ink as
stain)
•C. neoformans deposits melanin (via
phenoloxidase) when grown in media
(bird seed agar) containing certain
catecholamines
•Fluconazole in AIDS
pts. used
prophylactically is
effecetive @ preventing
infection
Immunology/Serologic Tests:
•Latex Agglutination Test reveals
presence of capsular antigenic material
from spinal fluid, urine, or serum (93%
sensitive, more reliable than India ink
smear of spinal fluid)
Histoplasma capsulatum (var. capsulatum)
Histoplasmosis
3 varietiesof H.
capsulatum:
1. var. capsulatum
2. var. duboisii
3. var. farciminosum
•Variety of clinical
manifestations
•Primary disease may be
asymptomatic, subclinical, or a
self-limited pulmonary disease
of varying degrees of severity
that leaves multiple areas of
calcification
•Dissemination (rare) »
emaciation leukopenia,
hepatosplenomegaly, and
irregular fevers
Source: (worldwide)
•intensity in USA, esp. around major
river valleys of Missouri,
Mississippi, & Ohio rivers
•organism can be isolated from soils
contaminated w/ bird droppings (esp.
chickens & starlings) and also bats
•Animals other than humans can
become infected: bats, cats, skunks,
etc. (does not cause disease in birds)
•Transmission: inhalation of
infectious microconidia from an
exogenous source (disease is
not contagious though)
•95% asymptomatic
•5% symptomatic
•All infected convert to positive
skin test though
Clinical Symptoms:
•influenza-like w/ fever &
pulmonary congestion (10-15%
cavitate)
•self-limiting in large portion of
cases
•Calcifications in the lung &
sometimes in the spleen are
common (cf. coccidioides)
•small percentage disseminate »
involvement of RES (liver,
spleen, lymph nodes) » hepatosplenomegaly common
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Dimorphism of H. capsulatum:
•37°C (in vivo & in vitro) = ovoid
budding yeast cell (blastoconidium)
•25°C (Room Temp, in vitro) = mycelium
w/ hyphae that produce characteristic
tuberculate macroconidia (with finger-like
projections on their walls) and small
spherical microconidia that are infectious
Appearance in Tissue:
•inhaled microconidia undergo
morphologic changes » direct budding »
blastoconidia » yeast cells in
mononuclear phagocytes in tissue (may
be extracellular, but organism is a
facultative intracellular parasite)
•Oral Ketoconazole for
progressive lung lesions
•Amphotericin B for
disseminated disease
•Oral itraconazole is
used to treat pulmonary
or disseminated disease,
as well as for chronic
suppression in AIDS pts
•only way to avoid is to
avoid travel to endemic
areas
MYCOLOGY
DISEASE
DEFINITIONS
EPIDEMIOLOGY
CLINICAL
LAB DX
THERAPY
•Transmission: inhalation of
infectious arthroconidia from an
exogenous source (disease is
not contagious though)
Dimorphism of C. immitis:
•37°C (in vivo & in vitro) = large
spherules containing many small
endospores
•25°C (Room Temp, in vitro) = mycelium
w/ hyphae that form arthroconidia that are
highly infectious (handle cultures w/
precaution)
•Amphotericin B for
persisting lung lesions
or disseminated disease
Coccidioides immitis
Coccidioidomycosis
(Valley Fever)
•Primary infection may be
asymptomatic, subclinical, or a
self-limited, pulmonary disease
of varying degrees of severity
•Dissemination in small
percentage of chronically ill »
chronic or acute malignant
disease that may involve nearly
any tissue of the body
Source:
•New World organism
•soil of North, Central, & South
America
•mostly SW USA - 10-15% outside
endemic area
• soil-inhabiting fungus of semiarid
regions (alkaline soil, freedom from
severe frosts, very hot, dry season
followed by some rain = good)
•Significant difference among the
ethnic groups w/ regard to likelihood
of disseminated disease (Filipinos
especially susceptible due to
assumptive genetic differences)
•60% asymptomatic
•40% symptomatic
•All infected convert to positive
skin test though
Clinical Symptoms:
•influenza-like (mild to severe)
•self-limiting in large portion of
cases
•15% cavitate
•small percentage disseminate
Appearance in Tissue:
•endospore-filled spherule found in
tissue or exudates (sputum, CSF, pus)
•spherules rupture » release of endospores
» cycle of enlargement & nuclear
replication
General Immunology:
•antigens are obtained from culture
filtrates of both saprobic (mycelial) &
parasitic (spherules) forms
•saprobic growth filtrate = coccidioidin
(most commonly used)
•parasitic growth filtrate = spherulin
Serologic & Immunologic Tests:
1. The Skin Test: inject coccidioidin (or
spherulin) intradermally » rxn measures
delayed type hypersensitivity (DTH) to C.
immitis antigens
•takes 3 wks to develop + test
•Negative due to: too early, not
coccidioidomycosis, or disseminated
(anergy)
•Positive: previous exposure (therefore
immune to second attack)
2. Antibody Tests: IgM, IgG, IgA, and
IgE classes
•Tube Preciptin (TP): TP Ab of IgM
isotype seen early in symptomatic illness
and then wanes
•Complement Fixation (CF): CF Ab of
IgG isotype is produced later in disease &
persists; titer correlated w/severity of
disease
Page 4
•Ketoconazole is also
effective in lung disease
•Fluconazole for
meningitis (intrathecal
Amphotericin B may be
required)
•only way to avoid is to
avoid travel to endemic
areas
MYCOLOGY
DISEASE
DEFINITIONS
EPIDEMIOLOGY
CLINICAL
LAB DX
Source: (worldwide)
•intensity in USA, esp. around major river
valleys of Missouri, Mississippi, & Ohio
rivers (like Histoplasma)
•males > females in numbers affected (10:1)
•some correlation w/occupation
•age & race are of no importance
•no reagent available for skin testing (so no
estimate of the # of asymptomatic or
subclinical cases)
•Transmission: inhalation of
infectious conidia from an exogenous
source (disease is not contagious
though)
Dimorphism of B. dermatitidis:
•37°C (in vivo & in vitro) = multiplies as
blastoconidia (which are much larger than those
of Histoplasma) w/thick cell walls & a wide base
@ the juncture of budding daughter cells
•25°C (Room Temp, in vitro) = white mycelium
w/ hyphae upon which are produced ovoid,
lateral conidia which are infectious
•teleomorphic form of growth as well
(Ajellomyces dermatitidis)
THERAPY
Blastomyces dermatitidis
Blastomycosis
•Chronic infection
•Primary disease is a pulmonary
infection acquired by inhalation of
infectious conidia
•Dissemination may involve any
part of body but marked predilection
for lungs, skin, and bone
Clinical Symptoms:
•first stage in infection is pulmonary
which may resolve spontaneously, but
does so less than pulmonary
coccidioido-mycosis and
histoplasmosis
•chronic infection of the skin (face,
leg, & foot) - may last many years
•lesions are suppurative granulomas
that heal spontaneously or by therapy
w/ pronounced scar formation
•Itraconazole for most
patients
•Amphotericin B for severe
disease
•Surgical excision may be
helpful
•no means of prevention
Appearance in Tissue:
•infectious conidia inhaled » large, solitary yeast
cells embedded in abscesses w/single buds that
have a broad basal attachment to the mother cell
•generally not intracellular
PURELY OPPORTUNISTIC INFECTIONS
Aspergillus species (esp. Aspergillus fumigatus)
Aspergillosis
•Aspergillus spp. exist only as
molds (they are not dimorphic)
•Aspergillus spp. produce blastic
conidia arranged on a special
conidiophore
•cause pulmonary infections of a
localized or invasive type (rarely
disseminated), allergy, or toxemias
due to ingestion of secondary
metabolites
•Also, imp. causes of pulmonary
disease in wild & domesticated
animals & a cause of mycotic
abortion in cattle
Source: (worldwide)
•all ages & sexes
•becoming increasingly important as
pathogens of immunocompromised hosts
Transmission:
•by airborne conidia
Interact with animal hosts:
1. by inducing allergies
2. by infectious invasion of tissues
3. by forming toxins that contaminate feed or food & induce
toxemias in those who ingest the
products
3 General forms of disease:
1. Pulmonary aspergillosis: rare in
immunocompetent, but extraordinarily
common in birds (chickens, penguins)
2. Cavitary colonization:
Aspergillus not uncommonly
colonizes pulmonary cavities formed
by other diseases (“fungus ball”)
3. Disseminated aspergillosis:
occurs in immunocompromised hosts;
route= pulmonary » skin, CNS, heart,
lung, & nasal-orbital areas; Surgical
contamination/inoculation may also
occur
Page 5
A. fumigatus as example:
Appearance in Cultures:
•produces a moderately fast growing, flat,
velvety, bluish green colony, becoming brown on
aging
•chains of enteroblastic phialoconidia produced
by one row of phialides pointing upward from the
upper part of the vesicle
Appearance in Tissue:
•Septate hyphae that branch @ acute angles
•Amphotericin B for
invasive aspergillosis, but
results may be poor
•Surgical removal of
fungus ball