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UNIT VI FUNGAL AGENTS OF DISEASES

AGENTS OF CUTANEOUS MYCOSES


SUPERFICIAL MYCOSES No Ab, no immune response, no inflamm reaction, In vivo = yeast & mold
Phaeoannellomyces weneckii/ Piedraia hortae Trichosporon beigelli/ Malassezia furfur/
Cladosporium werneckii/ Exophiala werneckii T. cutaneum Pityrosporum furfur/ P. orbiculare/ P.ovale
Tinea nigra (keratomycosis nigricans palmaris/ Black piedra White piedra Tinea versicolor/ pityriasis versicolor/ liper spot/
Pityriasis nigra/ microsporosis nigra) dermatomycosis furfuracea/ chromophytosis

Brown to black nonscaly macules on the palms & soles hard, dark brown to black gritty nodules on scalp hair, Soft, white, yellowish, beige or greenish nodules on hair patchy lesions/scaling of varying pigmentation fawn
~melanomas beard, moustache, axillary/pubic hairs shafts colored liver spots on the chest, trunk, abdomen
soft mycelial mat around facial & genital hair, hair scalp
Found in soil Nature, normal skin flora
infects horse
VIA : Trauma to superficial layer of the skin
KOH MOUNTS KOH MOUNTS KOH MOUNT
Fungus : long strands of septae, dematiaceous hyphae nodules crushed to reveal asci (thick walled rhomboid intertwined hyaline septate hyphae Skin scraping
*may contain numerous chlamydospores cells with 8 ascopores) hyphae breaking up into oval/rectangular arthroconidia yellow fluorescence on woods lamp
2-4um diameter

CULTURE CULTURE CULTURE CULTURE (not essential)


SDA : 2-3weeks (slow) SDA + antibiotics (room temp) Chloramphenicol (cycloheximide = inhibitory) olive oil + medium incubation 37C
Colonies : moist, olive to greenish black , yeast like Colonies: dark brown with dematiaceous septate hyphae Colonies: rapid growth, cream colored, soft when young, Budding yeast
Cycloheximide = inhibitory membranous and wrinkled when age
MICROSCOPIC EXAM budding blastoconidia and arthrocodnidia MICROSCOPIC EXAM
Colonies: 1 to 2 celled cylindrical to spindle shaped cells Spaghetti and meatballs
budding /annelid formation ***Conidia & ascopores = not found on routine mycological BIOCHEMICAL TEST budding yeast along with septate, sometimes branched
rounded at 1 end and tapered toward the other media Doesnt ferment CHO & KNO3 hyphae
occl mycelial Assimilates glucose, galactose, sucrose, maltose, lactose hyphae are not demonstrated on routine media
TREATMENT Urease (+)
removal of infected hair shafts TREATMENT
applicaton of topical fungicides CM 1% selenium sulfide (temporary)
Pneumonia/ non specific febrile illness
may cause fatal systemic infection Associated diseases: folliculitis, obstructive dacrocystitis,
seborrheic dermatitis in AIDS

DERMATOPHYTOSES Keratinophilic: grow on layers of hair, nails, skin (contain keratin) HOST REFERENCES:
immune response, inflammation, tissue damage, ring worms Host reaction to metabolic products of fungus 1. Zoophilic Adapted to living on animals
Genera: Microsporum, Trichophyton, Epidermophyton, 2. Anthropophilic Adapted exclusively to human hosts
3. Geophilic Inhabits the soil
Tinea Barbae Tinea Capitis Tinea Corporis Tinea Cruris Tinea Favosa Tinea Imbricata Tinea manuum Tinea Pedis Tinea Unguium
Beard/ Barbers itch Head/scalp Body glabrous skin Groin Head Body Hand feet Nails
T. mentagrophytes Gray patch T. rubrum, T. tonsurans E. floccosum T. schoenleinii, (distinctive lesion) T. mentagrophytes T. mentagrophytes
Farm workers M. auduinii/ M. canis M. canis, M. gypseum Circinate and T. violaceum T. rubrum T. rubrum
Inflammatory lesion Ectothrix infection in child Occl serpiginous lession cup shaped crusts, E. floccosum E. floccosum
Inflammatory ecothrix Anular leson on the skin inflammatory, prominent honey Athletes foot, mocassin foot Lateral/distal edges
T. mentagrophytes smooth parts of body vesicular, enlarging comb like masses itching, scaling, seeping skin of nail plate
Animal origin spreading, hemorrhagic margins lesion on the soles of the feet paroncychial
Black dot (endothrix infection) border VIA : clothing, linens, & cleft betweent the toes infection
T. tonsurans towels shared Thickened nail,
Kerions brittle with
T. tonsurans accumulation of
Fungating exophytic masses subungual keratinized
Favus (tnea favosa) debris
T. schoenleinii, T. violaceum
cup shaped crusts, prominent honey
comb like masses
COMMONLY ENCOUNTERED DERMATOPHYTES
EPIDERMOPHYTON MICROSPORUM
E. floccosum M. audouinii M. canis M. Ferugineum M. gypseum
Anthrophophilic Antropophilic Ectothrix infection of the hair Ectothrix, Tinea capitis Ectothrix, Tinea barbae
infects skin, nail Zoophilic Anthropophilic
most common cause of ringworms in cats and dogs WOODS LAMP
Hyphae: thick septa Doesnt fluoresce
CULTURE CULTURE CULTURE : Potato dextrose agar (bamboo)
Colonies: yellow to yellow green (olive drab) and quite Isolate: Chlamydoconidium like swellings Colonies: lemon-yellow Macroconidia : fusiform, thick walled, 6 cells
wrinkled/folded terminally on hyphae Macronconidia: spindle shaped, echinulate, thick walls, Distal area : thin, filamentous tail, longer than
Microconidia : none Favic chandeliers, pectinate bodies tapered/curved ends the rest of conidium
Macroconidia: smooth, thin walled, single/cluster Macroconidia : rare, bizaar (3-15 cells) ***hair baiting
Distal end: broad, spatulate/ club shaped (beavers tail) Doesnt grow on rice Microconidia : rare
***Grows on rice!!

WOODS LAMP : Fluoresce green

TRICHOPHYTON
T. concentricum T. mentagrophytes T. rubrum T. schoenleinii T. tonsurans T. verrucosum T. violaceum
T. imbricata Athletes foot T. corporis, T. ingium, T. capitis T. favosa Tinea capitis (black dot) T. corporis, T. barbae, T. capitis T. favosa
anthropophilic Zoophilic, anthropophilic endothrix Favic chandelier and anthropophilic Found in cattle
skin Most commonly isolated anthropophilic chlamydospores VIA: fomites
dermatophyte
Infect: skin, hair, nails
CULTURE CULTURE CULTURE CULTURE CULTURE 35C CULTURE
Spiral hyphae Colonies: red, + brown mix Colonies: slow (30days) SDA Thiamine Colonies: violet/ purple and
Macroconidia: thin walled, Macroconidia: 3-8cell, Small, wrinkled, waxy Colonies: rust colored on the Macroconidia: thin walled, waxy
smooth, cigar shaped 4-5 cell cylindrical, pencil shaped reverse side string beans/ rat tails Thiamine: enhancer
Microconidia: globose to tear Microconidia: clavate, peg Thiamine microconidia: clavate, hyphae: swollen w/ granules
shaped (grape like) Macroconidia: teardrop peg teardrop
WOODS LAMP Microconidia: rare, balloon
5 DAY UREASE (+) Doesnt fluoresce WOODS LAMP
Doesnt fluoresce
HAIR PENETRATION TEST HAIR PENETRATION TEST
Perpendicular penetration peg Surface erosion

MYCOTOXINS TOXIC METABOLITES PRODUCED BY FUNGI


AFLATOXIN VOMITOXIN (Fusarium spp)
A.fla + toxin
Molds: A.flavus, A. parasiticus, Penicillium spp, Rhizopus spp PATULIN (P. expansum)
Aflatoxifcosis : human, dogs ingestion of apple juice
jaundice, ascites, portal hypertension, high mortality
massive GIT death
pulmonary interstitial fibrosis
factor of reyes syndrome
carcinogen

OCHRATOXIN (A. alutaceus, Penicillium spp)


acute toxicity (kidney), balcan (nephropathy)
carcinogen

FUMONISN (F. verticilhoides)


esophageal cancer

TICHOTHECENES (F. graminearum)


acute toxicity and immune suppression
SUBCUTANEOUS MYCOSES
CHROMOBLASTOMYCOSIS EUMYCOTIC MYCETOMA SPOROTRICHOSIS SUBCUTANEOUS PHAEOHYPHOMYCOSIS
EPIDEMIOLOGY EPIDEMIOLOGY EPIDEMIOLOGY EPIDEMIOLOGY
Fonsecaea compacta, Phialophora verrucosa, Fonsecaea pedrosoi, Pseudallescheria boydii, Acremonium falciforme, Madurella Sporothrix schenckii Exophiala jeanselmei, Wangiella
Cladophialophora carrioni ,Rhinocladiella aquaspersa mycetomatis, Madurella grisea, Exophiala jeanselmei Found in soil dermatitidis, Cladosporium trichoides,
Verrucous dermatitis and chromomycosis true fungi Asso : gardeners disease Phialophora spp, Dreschlera spicifera,
VIA: exposure to rose throns (rose handlers dse) and Hormodendrum spp
sphagnum moss Dermatiaceous fungi
CLINICAL INFECTIONS CLINICAL INFECTIONS CLINICAL INFECTIONS CLINICAL INFECTION
Chronic infection of the skin & subcutaneous tissu Lesion: granulomas, tumor like, abscesses drain to the outside 1. Extracutaneous/ Disseminated sporotrichosis 1. Deep tissue invasion
Lesion: confined to the extremities (feet, legs), verrucous nodules through sinus tract for the immunocompromised most serious
(may be ulcerated and crusted) Lesion pus: granules/grains (compact mycelial masses) 2. Fixed cutaneous deep draining systemic abscess
longstanding lesion: cauliflower like surface initially confied to subcutaneous tissue infection is confined to the site of innoculation serebral chromoblastomycosis
frequently proliferate to involve the musculature and can cause 3. Lymphocutaneous 2. Ethmoid invasion
severe bone destruction Nodular & ulcerative lesion along lymph channels massive invation
===GRANULES Drain the primary site of inoculation subsequent erosion of ethmoid bone
Fungus Color Size mm Texture 4. Mucocutaneous 3. Subcutaneous cysts
P. boydii White 0.5-1.0 Soft 5. Primary and secondary pulmonary sporotrichosis single, firm, discrete, well defined nodule
A. falciforme 0.2-0.5 Soft little pain
M. mycetomatis Black 0.5-5.0 Hard foreign body first impression
M. grisea 0.3-0.6 Soft lesions: spread, verrucous, simulate
E. jeanselmei 0.2-0.3 soft
chromomycosis
LABORATORY DIAGNOSIS LABORATORY DIAGNOSIS LABORATORY DIAGNOSIS LABORATORY DIAGNOSIS
Specimen collection Specimen collection Specimen collection Specimen collection
Punch biopsy: affected skin area Granules: color, size, texture Aspirates: cutaneous nodules, pus, exudate Biopsy : dematieous hyphae
=====Direct examination Swabs: open lesion
skin biopsy: sclerotic/ copper bodies Direct microscopic exam Curettage material Microscopic exam
Hyphal elements: seen GMA, H&E, PAS, Masson fontana stains
Microscopic examination easily distinguished from the branching filamentous rods in Direct microscopic exam detect melanin in the cell wall
Cladosporium Erect conidiophores (branched, 1 cell, brown blastoconidia) actinomycotic mycetomas small cigar shaped yeast
Conidium close to tip of conidiophore (shield cell)
carrioni
Fragile chains
Culture
Fonsecaea ~F. pedrosoi Culture Culture a) Exophiala jeanselmei
compacta More compact conidial heads P. boydii PDA 25C & 35C dimorphic 25C and 37C incubation doesnt grow at 40C
Conidia are subglobose Rapid, white to dark gray
**S.apiospermum (anamorph) = oval conidia, single, tips of
Cycloheximide nitrate (+)
Fonsecaea Primary 1 cell conidia on sympodial conidiophores
Primary conidia : conidiogenous cell secondary conidia annelids a) 25C b) Wangiella dermatitides
pedrosoi
Phialophora Condiogenous cells dematiaceous
**Teleomorphs = cleistothecia w/ ascopores initially : white, glabrous, yeast like Grow at 40C
A. falciforme Moniliaceous/light colored mold
verrucosa Flask shaped phialides w/ collarettes later: darker, mycelial Nitrate (-)
Slow, grayish brown graying violet
Conidia oval, 1 cell, in balls at tips of phialides hyphae: thin, delicate with conidia in have phialides without colarettes
Mucoid clusters of 1 or 2 cell
Rhinocladiella Conidiophores erect, dark, bearing conidia only on upper portion
near the tip
Slightly curved conidia borne from phialides rosette/flowerette pattern at the ends of
aquaspersa Conidiophores: long, unbranched, multiseptate
Conidia elliptical, 1 cell, sympodially conidiophores
M. 37C & 40C
Slow, white yellow, olivaceous/brown, diffusable brown Conidia: dark walled/dematiaceous, along the sides of
Culture mycetomatis Conidia: half of isolate from the tips of phialides hyphae, sleeve arrangements
Half of isolate : sterile b) 37C
darkly pigmented / dematiaceous molds
M. grisea 30C
slow growth Slow, olive brown to black BA tubes 37C
velvety to wooly, gray bron to olivaceous black Reddish brown pigment require several subcultures
E. Doesnt grow at 40C cigar shaped yeast cells
Olivaceous to black color, initially yeast like, mature to velvety
jeanselmei Conidia: born from annellides aggregating in masses
Nitrate (+)

EXO ANTIGEN TEST


Isolate + BHI broth
Ag are extracted from supernatant using merthiolate
detect Ag : immunodiffusion technique
ENDEMIC MYCOSES (SYSTEMIC/DEEP SEATED)
GEN CHAR: All dimorphic, VIA: inhalation of infectious conidia, all lab procedure: biologic safety cabinets
Blastomyces dermatitidis Coccidiodes immitis & Coccidiodes posadasii Histoplasma capsulatum var capsulatum Paracoccidiodes brasiliensis
/ Ajellomyces dermatitidis / Emmonsiella capsulata
EPIDEMIOLOGY EPIDEMIOLOGY EPIDEMIOLOGY EPIDEMIOLOGY
Blastomycosis disease (Gilchrist dse, NA blastomycosis, Coccidiomycosis (Posada dse, coccidiodal granuloma, Histoplasmosis (reticuloendothelial cytomycosis, cave Paracoccidioidomycosis (SA blastomycosis, Brazilian
Chicago dse) valley fever, desert rheumatism, valley bumps, California dse, spelunkers dse, darling dse) blastomycosis, lutz splendore almeida dse, paracoccidiodal
From soil, decaying wood dse, San joaquin valley fever) From soil with high nitrogen content (heavily granuloma)
Affect human, dogs, horses contaminated with bird & bat guano) sex distribution 9:1
CLINICAL INFECTION CLINICAL INFECTION CLINICAL INFECTION CLINICAL INFECTION
1. Pulmonary most virulent of all mycotic agent Inhaled microconidia phagocytosis by macro in Primary infection: asymptomatic, may disseminate
initial mild respiratory symptoms: fever, cough, primary dse: resolves w/o therapy, confers a strong pulmonary parenchyma leading to ulcerative lesion of the buccal, nasal, GI mucosa
hoarseness specific immunity (Coccidiodin skin test) 1. Primary acute Lymph node is involved
progression: few months: productive cough, fever, weight symptomatic/flu like symptoms, chest pain, shortness of Dissemination to other organs: adrenals, diminished host
loss 1. Asymptomatic pulmonary dse breath, hoarseness defenses
2. Systemic 2. Allergic manifestation diffuse/discreet lung lesion : calcify
extension -toxic erythema almost always skin test (+)
common site: liver, spleen -erythema nodosum (desert bumps) 2. Chronic cavitary
granulomatous lesions & abscess -erythema multiforme (valley fever) large pulmonary lesion after discomfort
3. Cutaneous -arthritis (desert rheumatism) ~~tuberculosis
either from direct inoculation or systemic dse 3. Symptomatic dse may progress to disseminated form
a) Primary 3. Severe disseminated
fever, respiratory distress, cough, anorexia, headache, organ involved
malaise, myalgias (6 weeks/longer) fatal in massive dissemination
b) Secondary dse
nodules, cavitary dse, progressive pulmonary dse Others: mediastinitis, pericarditis, mucocutaneous lesion
single/multisystem dissemination 1%
Filipinos, African american
9:1 female:male
LABORATORY DIAGNOSIS LABORATORY DIAGNOSIS LABORATORY DIAGNOSIS LABORATORY DIAGNOSIS
Specimen collection Specimen collection Specimen collection Specimen collection
1st morning sputum Sputum sputum Sputum
bronchial washign tracheal aspirates bronchoscopic fluid Bronchoalveolar lavage
pulmonary secretion lung biopsy tissue BM aspirates Pus from draining lymph nodes
CSF peripheral blood smear scrapings from ulcers
Direct Microscopic exam Blood exudate from mucocutaneous lesion biopsy tissue
Large, spherical, refractile yeast cell (8-15um) exudate from liver and spleen
double contoured wall Direct microscopic examination Direct microscopic exam
buds connected by a broad base Spherules w/ endospores Direct microscopic exam budding yeast (15-30 um) with multipolar
(produced by inhaled barrel shaped arthroconidia) small yeast cell budding at the periphery (mariners wheel)
Culture common within monocytes and macrophages daughter cell : connected by narrow base
Inhibitor: cycloheximide Culture non encapsulated, looks like encapsulated mickey mouse cap appearance
Heavily contaminated = plate on media with antibacterial initial: 3-4 days, white to gray, moist, glabrous
a) 25C mature: abundant aerial mycelia, enlarged colony in a Culture Culture
white, tan, brown circular bloom. Become tan to brown to lavander 2 Sets of SDA, BHI/ inhibitory mold agar a) 25C
fluffy to glabrous in concentric rings hyaline arthroconidia: separated by disjunctor cells 25C & 37C colonies: flat, glabrous to leathery, wrinkled to folded,
raised areas (spicules/prickles) in the centers of colonies Exoantigen test white to brownish mold floccose to velvety, pink to biege to brown with yellowish
anamorphic : conidia born/short lateral branches, ovoid young: round to pyriform microconidia (2-5um) brown reverse
to dumb bell shaped. Short conidiophores~ lollipops mature: large echinulate to tuberculate macroconidia small 1 cell conidia
teleomorphs (A.dermatitidis) : doesnt occur in routine confirm: BHI 37C, conversion of mold to yeast exoantigen test
---produce gymnothecia w/ ascopores Exoantigen detection: detect H & M antigen
Exoantigen technique: Kaufman, standard = b) 37C
Detects cell-free antigen in mycelial form using rapid conversion with BHI blood
Immunodiffusion test
Complement fixation , Immunodiffusion for sero
b) 37C diagnosis
broad based yeast cell
OPPORTUNISTIC MYCOSES = Cant produce disease in immunocompetent
Gen char: ubiquitous agent, part of normal flora, monomorphic mostly, px: immunocompromised
Aspergillus spp Candida albicans Cryptococcus neoformans Hyaline, Septate, Monomorphic Penicillium marneffei Pneumocystis jiroveci (P. Zygomcetes
A. fumigatus, A. flavus, A. niger, A. terreus C.tropicalis, C.parapsilosis, C.glabrata Teleomorph Filobasidiella neoformans molds carinii) Rhizopus, Mucos, Absidia
EPIDEMIOLOGY EPIDEMIOLOGY EPIDEMIOLOGY EPIDEMIOLOGY EPIDEMIOLOGY EPIDEMIOLOGY EPIDEMIOLOGY
Aspergillosis Candidiasis (moniliasis, mycotic Cryptococcosis (torulosis, Asso fungemia, disseminated Dimorphic fungus endemic in immunocompromised px Sparsely septate, hyaline
Found worldwide vulvovaginitis, thrush, european blastomycosis) infection, mycotic keratitis, southeast asia dissemination : rare monomorphic molds
Normal saprophyte in soil candidiosis, candida Found in soil (pigeon droppings) endopthalmitis, skin infection, asso with bamboo rat only in AIDS immunocompromised px
Carcinogenic hapatoxin: endocarditis) endocarditis VIAUNKNOWN prev : protozoan diabetes melitus px
aflatoxin most frequently encountered cell membrane: cholesterol foundin decaying vege
abundant in environment may be normal flora matter and soil
VIA: inhalation of spores
common bread molds
CLINICAL INFECTION CLINICAL INFECTION CLINICAL INFECTION 1. Acremonium CLINICAL INFECTION CLINICAL INFECTION CLINICAL INFECTION
1. Allergic forms 1. Cutaneous & Mucosal 1. Acute/ Chronic pulmonary Septate hyphae 1. Focal Cutaneous infection Morphologic forms: 1. GI
a) allergic bronchopulmonary candidiasis -transitory/pass unrecognized unbranched, tube like phialides 2. Mucocutaneous infection 1. Trophozoltes 2. Perineural invasion
aspergillosis Risk factor: AIDS, pregnancy, -asymptomatici infection produce clusters of 1 cell & 3. Disseminated infection predominant 3. Rhinocerebral form
b) extrinsic allergic alveolitis diabetes, young/old age, birth control 2. Systemic/ meningeal 2cell oblong conidia difficult ti ID massive necrosis with
2. Aspergilloma (fungus ball) pills, trauma, burns, skin maceration most common 2. Fusarium spp 2. Cysts vascular invasion and
---oral thrush, onychomycosis,
inhaled conidia enter exisiting intertrigenous infection (most/warm
from meningitis 1 cell microconidia pingpong ball infarction
cavity parts of body), interdigital infection, sickle /boat shaped 4. Respiratory
rarely invasive vulvovaginitis macroconidia + septation 10:1 5. Skin & subcutaneous
found in lungs 2. Systemic Candidiasis 3. Geotrichum Troph:cysts infections
3. Extrapulmonary colonization via indwelling catheters, surgery, IV septate hyphae
4. Invasive aspergillosis drug abuse, damage to skin/GIT barrel shaped non alternating
5. External otomycosis, mycotic Asso with chronic admin of arthroconidia, no blastoconidia
keratis, onychomycosis immunosuppressive drugs 4. Paecilomyces
6. Eye & hair infection 3. Chronic mucocutaneous long, delicate penicillus
candidiasis produce numerous chains of
chronic superficial disfiguring
infeaction of sking & mucosa area
small, oval conidia, easily
onset : early childhood dislodged
LABORATORY METHODS LABORATORY METHODS LABORATORY METHODS 5. Scopulariopsis LABORATORY METHODS LABORATORY METHODS LABORATORY METHODS
==Specimen Collection== ==Specimen collection== ==Specimen collection== produce penicillus with large, ==Specimen collection== ==clinical presentation== ==Direct Microscopic exam=
Sputum Swabs & scrapings: superficial lesion CSF = most common flat based, rough walled conidia Infected tissue/exudate branching coenoctic hyphae
Respiratory specimen blood serum/CSF for Ag detection ==radiographic studies==
Blood (rarely (+)) spinal fluid (Latex agg.test) = most sensitive ==Direct Microscopic exam= ==Culture==
tissue biopsy
urine
Small yeast like cells with ==Direct Microscopic exam= 1. Absidia
==Direct microscopic exam== exudate ==Direct Microscopic exam= internal crosswalls respiratory spn pyriform sporangia + funnel
Hyphae & hyaline = septate material from removed IV catheter encapsulated yeast in india ink no budding cells produced shaped apophysis
==Culture== 2. Mucor
==Culture== ==Direct Microscopic exam= ==Culture== 37C ==Culture== SDA No growth no rhizoids/stolons
incubation = room temp gram stained smears: Mucoid colonies blue-green to yellowish 3. Rhizopus
ID: morphology of conidial Pseudohyphae, budding cells inhibitor : cycloheximide colonies unbranched sporangiospores
stucture skin/nail scrapping + 10% KOH Urease (+) Soluble red to maroon pigment with rhizoids appearing at the
dark to brown spores Yeast ID system on reverse side of colony point where stolon arises
==Culture== 37C BHI/MH Mycelial to yeast conversion
non selective agar media (2 weeks)
yeast colony = pseudohyphae mycelial produces brushlike
Germ tube test (+) conidiophores (penicillus)
Serum + Rg (2-4hr)
Chlamydospores in cornmeal
agar (RT 3-5days =
pseudohyphae)
Urease (+)
CHROMagar: differential med.
Carbs assimilation test
API 20C AUX = Gold std.