MYCOSIS SYSTEMIK

Oleh :

Efrida Warganegara
 Overview Fungi
Mycology study of fungi
Fungi include :
1) Yeast : single-celled fungi
2) Mold : filamentous fungi
3) Mushrooms : simply the reproductive structures
of certain fungi
Fungi are characteristic by a cell wall that contain
chitin (the same molecule in exoskeleton in insect;
chemically distinct from peptidoglycan in bacteri)
unaffected by antibiotic that inhibit peptidoglyban
synthesis
Fungal membranes typically have ergosterol
(distinguishing from animal cell membrane,;which have
cholesterol) ergosterol is target for many
antifungal medication
 Medical Importance of Fungi
Fungi cause human illness in three
general ways :
1) person develop an allergic or asthmatic
reaction to the fungus or its spores;
2) grow on or in the human body
Mycosis causes fungal disease;
3) produce toxin that a person ingests
a. Aflatoxin (Aspergillus sp.)carcinogeic
b. Ergot hallucinogenic; ergotamin
decrease blood flow
 Mycosis
Mycosis (human fungal disease) are classified
by location on or in the body where the
infection occurs
Cutaneus Mycosis when limited to the
epidermis
Subcutaneus Mycosis when the
ingection penetrates significantly beneath the
skin
Systemic Mycosis when the infection is
deep within the body or dessiminated to
internal organ
(Harvey,2007)
 Mycosis Systemic
* Introduction
The m.o. responsible for systemic mycosis
2 general categories :
1) those that infect normal healthy individuals
(true pathogens); and
2) those that primarily infect debilated, and /
or immunocompromized individualis
(opportunistic pathogens).
In the US the most common systemic
mycotic infections are coccidioidomycosis,
histoplasmosis, and blastomycosis in the
immunokompetent host
Mycosis Systemic - Pathogens
* Introduction
These infection occur in defined geographic areas
where fungal pathogen are found in the soil and can
be aerosolized.
Clinical manifestation closely resemble those seen in
tuberculosis :
- in that asymptomatic primary pulmonary
infection is common,
- whereas chronic pulmonary or dessiminated
infection is rare
The fungi causing these disease are :
- uniformly dimorphic,
- exhibiting the yeast form in the tissue, and the
mycelial form in culture or in their natural
environment
A. Epidemiology and pathology
Entry into host is by inhalation of
airborne spores which
germinate in the lungs
From the lung, dissemination can
occur to any organ of the body
where the fungi can invade and
destroy tissue (figure)
 B. Clinical Significance
In spite of potentially systemic disease,
most cases of coccidioidomycosis,
histoplasmosis, Blastomycosis and
para coccidioidomycosis, in healthy
patient present only mild symptom
and are self-limiting.
In immunosuppressed patient,
however, the same infection can be
life-threatening
 1. SYSTEMIC MYCOSIS :
Pathogenic
Disease Agent
Blastomycosis Blastomyces
dermatitidis
Histoplasmosis Histoplasma
capsulatum
Coccidioidomycosis Coccidioides
immitis
Paracoccidioidomycosis Paracoccidoides
brasiliansis
B. Clinical Significance
1. Coccidioidomycosis
- Etiology : Coccidioides immitis
- Most cases in southwestern US and central and
South America
- In Soil : the fungus generates spores by septation
of hyphal fillament (arthrospores) spore become
readily airborne enter the lungs,
- where they germinate and develops into large
spherules filled with many endospores.
- Rupture of the spherule release the endospores,
each of which can form a new spherule.
-- In cases if disseminated disease, lessions occur
most often in the bones and the CNS (meningitis)
 1. COCCIDIOIDOMYCOSIS
= valley fever
Etiologic agent : Coccidioides immitis,
a biphasic fungal pathogen
Epidemiology :
C. immitis grows in semi-acrid, solid, is
known to exist in North, Central, &
South American, especially California; its
inhaled into the alveoli, where it
produces disease, either benign (
resembles flu ), or acute, depending on
many factors ( race; inoculum )
 1. COCCIDIOIDOMYCOSIS
= valley fever

Clinical features :
most is a benign disease, prodeces
only mild symptoms; among certain
races ( Filipinos, Black ), immuno-
supressed or the used of corticosteroids,
- disseminated may occur
there is no site of predilection for
this organism; any body tissue may
become infected
 1. COCCIDIOIDOMYCOSIS
Laboratory diagnosis :
Direct microscopic examination :
wet mount : specimens in KOH mounts, C.
immitis may be seen as sporangia
( spherula ) filled with endospora
histophatology
: the sporangia stain well
with HE & PAS stain
 1. COCCIDIOIDOMYCOSIS
Culture : Never work with culture on the laboratory
bench OUTSIDE of a biohazard hood !
C. immitis is a biphasic fungal phatogen, grows at room
temperature repidly producing a dirty gray-white
colony; at maturity, the hyphae develops arthroconidia
wich enlarged & barrel-shaped; alternate cells empty the
hyphae break easilly into separate artrhoconidia
float in the air spread by the wind

Serology : used as diagnostic & prognostic tools; include

CFT, latex aglutination, ID test
Treatment : Amphotericin B, Ketoconazol
 2. HISTOPLASMOSIS
= reticuloendotheliosis
= Darlings disease
Etiologic agent : Histoplasma capsulatum, a
dimorphic fungus, having a mold form at room
temperature & yeast form at 370C
Epidemiology :
H. capsulatum grows in soil, especially in soil that
enriched with bat or bird manure
often be isolated from old building/caves, where
birds/chickens or bats have roosted
H. capsulatum grows in soil in the mycelial form &
large number of conidia are produce
the disease is acquired by inhaling conidia &
reported from most area of the world
 HISTOPLASMOSIS
Clinical features :
is primarily a pulmonary disease; when conidia are inhaled,
infections is established in the lungs; the disease may be mild, with
few or no symptom (95%)
may be severe with lung infiltrates, from mild to extensive
primary pulmonary histoplasmosis progresses to chronic
pulmonary disease in about 5 % of those with disease; is
characterized by fibrosis & cavitation,
symptoms includes : cough, fever, chills & weight lose (resembles to
toberculosis, sarcoidosis, & other systemic fungal disease)
the most severe form of histoplasmosis is disseminated disease; the
fungus invade any organs of body
HISTOPLASMOSIS
Laboratory diagnosis :
Direct microskopic examination : wet mount :
H. capsulatum may be seen in sputum, bronchial
washed, or in any body fluids as a small yeast, 4 - 6
um
histopathology : the yeast form can be found in tissue
removed from the infected sites, ussually in the
macrophage & in granulomas
GMS (gomori methenamine silver) stain should be
used ( the yeat dark-brown - black )
 HISTOPLASMOSIS
Culture :
colony morphology : H. capsulatum grows slowly in the mold
form when incubated at room temperature, appear in 7 - 10 days
but conidia is not form until later; on SDA ( sabouraud dextrose
agar ) the colony Is ussually white & cottony
microscopic morphology :
two types of conidia are prodeced by H. capsulatum small,
pyriform smoth-walled conidia (microconidia, 4 - 6 um )
and large, round, thick-waled tuberculated conidia
(macroconidia, 8 - 18 um ) the diagnostic conidia
to prove the identification of H. capsulatum, convert the
mold form - yeast form; be done by transferring the mold
colony to blood agar & incubate at 370C in 3 - 5 days the
yeast colony will be white brown
 HISTOPLASMOSIS
Serology :

antibodies to the fungus are produced within 10 - 21

days after a person is infected by H. capsulatum
agglutination test, measures IgM antibodies, is a
quantitative test
CFT, measures both IgM & IgG, is quantitative test; ID
test is a quantitative test

Treatment :
Amphotericin B, Ketoconazole
 3. BLASTOMYCOSIS
= Notrh American Blastomycosis; = Gilchists disease

Etiologic agent :
Blastomyces dermatitidis, a dimorphic fungus that grows as
mold at room temperature and as a yeast at 35 - 370C
Epidemiology :
B. dermatitidis is saprophytic in nature & grows in the
mold form in soil; or decaying wood associated with
soil, has been isolated several times, but repeated
isolation from the same sites were not succesful
most of the cases have been found in Noth America, but
also prevalent in Africa & has been reported in India,
occurs most often in adult males
the lack of a specific skin test antigen has prevented the
 BLASTOMYCOSIS
Clinical features :
the primary site of Blastomycosis is the lung, with mild
infiltrat & few clinical symptoms
in severe disease, pulmonary infiltrate may be more
extensive & the patients will have fever, cough & weight lose,
nodular pulmonary lesion may occur
some cases may progres to chronic disease with pulmonary
fibrosis & the cavitation
the fungus may disseminate to any organ of the body, mostly
skin & bone
skin lesion are frequently a manifestationof disseminated
disease, with dry & scaly, extensive granulomatous with
vesicle or pustule
 BLASTOMYCOSIS
Laboratory diagnosis :

Direct microscopic examination :

wet mount : B. dermatitidis appear as a large, thick-
walled single-budding yeast ( 8 - 18 um ), the bud
has a wide base
histophatology : the yeast form is usually easily
fount in infected tissue, are best detected with PAS
or GMS stain
 BLASTOMYCOSIS
Culture :
is the dimorphic fungus, that grows in the mycelial form
(mold) at room temperature & as a yeast at 370C
the mold form grows slowly, became visible in 7 - 10 days,
the colony is usually white & cottony
the yeast-like colony grows on blood agar at 370C after 3
- 4 days
Microscopic morpology :
the mold produces small, smooth walled conidia &
attached to the conidiophores that arise directly from the
hyphae
yaest are large, thick-walled, single-budding & the bud has
a wide base (neck) the diagnostic structure
of B. dermatitidis
 BLASTOMYCOSIS
Serology :

IDtest is the most reliable, CFT not detect

antibodies in all cases, will
cross-react with antibodies to H.
capsulatum

Treatment : Amphoterisin B, Ketoconazole

 4. PARACOCCIDIOIDOMYCOSIS
= South American blastomycosis

Etiologic agent : Paracoccidioides brasiliaensis,

a dimorphic fungus that grows as mold at room temperature &
as a yeast at 370C / in infected tissues

Epidemiology :
the saprophytic habitat of P. brasiliensis is not known; endemic
mostly in South America

most cases of paracodioidomycosis are seen in adult males; is rare

in children
& adult women; appears to reflect a host-parasite relasionship by
sex hormones
 PARACOCCIDIOIDOMYCOSIS
Clinical features :
the primarily site of infection is the lung; disease may be
benign, primary pulmonary form or may disseminate to
produce acute & chronic, progresive disease, includes
lymph nodes & skin
the primary benign form may ultimately results with some
residual interstitial fibrosis
acute & chronic, progresive paracoccidioidomycosis,
disseminated from of the disease, most prequently recognized
on the basic of lesion on oropharynx & gingivae
progresive chronic pulmonary disease may involve all
lobes of the lung; produce extensive fibrosis
 PARACOCCIDIOIDOMYCOSIS
Laboratory diagnosis :

Direct microscipic examination :

wet mount : appears a large, yeast-like cells ( 30 - 360 um
), budding with one or more buds ( multiple buds ) with
narrow necks

histophatology : in infected tissue appears as large cells,

multiple buds, connected to the parent cell by narrow
necks, it has been called a pilot wheel or mickey
mouse
 PARACOCCIDIOIDOMYCOSIS
Culture :
colony morphology : P. brasiliensis is a dimorphic fungus,
grows slowly in the mycelial form at room temperature;
readily convert to the yeast phase when grown at 370C
on enriched media
microscopic morphology : the mycelial form is thin,
septate hyphae, conidia, chlamydospora & arthroconidia
may be formed; yeast phase cultures will demonstrate
both mycelial element & yeast; the yeast are
characterized by large ( 30 um or more ); multiple-
thin-walled buds, with narrow necks
 PARACOCCIDIOIDOMYCOSIS
Laboratory diagnosis :

Serology : CFT & ID test have been

shown to be reliable; however cross
reactions may occur

Tretment : Ketoconazole, Amphotericin

B, Sulfadiazine
 SYSTEMIC MYCOSES
SYSTEMIC MYCOSIS : Opportunistic

Disease Agents
Candidiasis Candida albicans; Candida sp.

Cryptococcosis Cryptococcus neoformans

Aspergillosis Aspergillus fumigatus;

Aspergillus sp.

Zygomycosis Mucor, Rhizopus, Absidia

 SYSTEMIC MYCOSES
Pathogenic Opportunistic

Agent : dimorphic fungus non-dimorphic fungus

Port dentre : lung (per inhalation) lung & others

Disease : usually chronic usually acute

Patients : could be healthy patients usually ill

patient
 SYSTEMIC MYCOSES
CANDIDIASIS = Candidosis
acute / chronic fungal infections, involving, the mouth,
vagina, skin nails, bronchi / lung, alimentary tract, urinary
tract, blood steam and less commonly, the heart or
meningen
are caused by Candida albicans or other species
are predisposed by : extremes of age, wasting, &
nutritional disease, excessive moisture, pregnancy,
diabetes, long-term antibiotics, & steroid use, indwelling
catheter, immunosupressed & AIDS
are generally treated with imidazoles, polyenes or both
 CANDIDIASIS
Candida albicans :
is part of the normal flora of the skin, mucous
membranes & GI tract along with other Candida
sp.
normal colonization must be distinguised from
infection
form elongated budding forms called
pseudohyphae, which are often seen in clinical
material along with true hyphae, blastoconidia &
yaest cells
 CANDIDIASIS
Clinical features : oral thrush
is a yeast infectoins of the oral mucocutaneus
membranes
manifest as white curd-like patches in the oral
cavity
occurs in premature infants; older infants being
treated with antibiotics, immunosuppressed
patients, long-term antibiotics & AIDS patients
 CANDIDIASIS
Clinical features : Vulvovaginitis
is a yeast infection of the vagina; manifest with a
thick yellow-white discharge, a burning
sensation, curd-like patches on the vaginal mucosa
& inflamation of perineum
is predisposed by diabetes, antibiotic therapy,
oral contraceptive use & pregnancy
may be transmitted to sexual partner as balanitis
 CANDIDIASIS
Clinical features : Cutaneus candidiasis
involves the nails (onychomycosis; paronychis ), skin
folds ( intertriginosa ) or groin ( such as diaper rash )
may be eczematoid or vesicular / pustular; is
predisposed by moist condition

Clinical feature : alimetary tract disease :

is usually an extension of oral thrush & may include
esophagitis & ultimately the entire gastrintestinal tract
is found in patients with AIDS or other
immunosuppressive disorder, particularly those patients
on long-term antibiotics therapy
 CANDIDIASIS
Clinical feature :

Chronic mucocutaneus candidiasis

is a chronic, often disfiguring, infections of the epithelial surfaces of
the body

is diagnosed microscipically & by the lack of cell mediated

immunity

Clinical feature :

Bronchopulmonary infections
occurs in patient with chronic lung disease; its usually manifested
by persistent cough
 CANDIDIASIS
Clinical feature :
Candidemia / blood borne infections
occurs most commonly in patients with indwelling
catheter; these infections are manifested by fever,
macronodular skin lesion & endopthalmitis

Clinical feature : Endocarditis

occurs in patient who have manipulated or damaged
valves, or in IV drug abusers

Clinical feature : Cerebrospinal infections

may occur in compromised patients
 CANDIDIASIS
Laboratory diagnosis :
direct microscopic examination : wet mount of the
skin / nail scraping or exudate, demonstration of the
presence of pseudohyphae / hyphae, & yeast in the tissue
culture : of the specimens on to SDA at room
temperature, Candida will grows as yaest-like colony
C. albicans be identified by :
* germ tube test -- yeast germination in serum at 370C
* culture on corn-meal-agar -- reveals chlamydospres
* culture on EMB-agar : reveals spider colony
* fermentation test of : glucose, lactose, maltose,sacharose
serologic : high levels of Candida precipitins or antigens
 SYSTEMIC MYCOSES : Opportunistic
CRIPTOCOCCOSIS
include subacute or chronic fungal infections involving
the lungs, meninges, or less commonly the skin, bones
& other tissues
most commonly occur as cryptococcal meningtis; often
occuring in AIDS patients
is caused by Cryptococcus neoformans; yeast that
posseses an antigenic polysaccharidae capsule
is associated with pigeon feces; considered to be an
opportunist in the present of underlying disease in
patients with Hodgkins disease, leukomias; or leucocyte
enzyme deficiency disease
 CRYPTOCOCCOSIS = Busse-Buschkes disease
= European Blastomycosis

Clinical feature :
pulmonary infections : are ussually
asymptomatic; & self resolving; most
common in pigeon breeder
meningitis ( most often ) or meningo-
encephalitis occurs in AIDS patients most
commonly with headache, ussually with
fever, followed by typical sign of meningitis
 CRYPTOCOCCOSIS
Laboratory diagnosis :
microscopic examination : wet mount,
demonstration of encapsulated yeast in CSF
sediment in india-ink
detection of the capsular material in the CSF
(the cryptococcal antigen ) by latex
agglutination test
culture : in SDA ( Sabouraud dextrase agar )
revealyeast colony
Treatment : Amphotericin B, 5- fluorocytosisn or
fluconazol
 SYSTEMIC MYCOSES : Opportunistic

ASPERGILLOSIS
caaused by Aspergillus fumigatus, an
opportunistic organism
is a ubiquitous filmentous fungus whose airborne
spores are contantly in the air
is recognized both in tissue & in culture by its
characteristic septate hyphae with
dichotomous branching, produced conidial heads
with numerous conidia
 ASPERGILLOSIS
Clinical feature :
Aspergilloma = fungus ball :
is a roughly spherical growth of Aspergillus
in pre existing lung cavities & does not
invade the lung tissue
occurs clinically as reccurent hemoptysis
& diagnosed by radiologig method

Treatment : surgical ( lobectomy )

 ASPERGILLOSIS
Clinical features : Invasive aspergillosis
occurs most commonly during severe netropenic in
leukemia & transplantm patients; most
commonly occurs as fever of unknown origin in
patient with neutropenia fewer than 500/mm3 &
pneumonia
it may begin as sinusitis or lungs; it disseminate to
any part of the body, most frequently brain
diagnosed by microscopy,culture of lung biopsy
is treated with amphotericin B or intraconzole &
has a high fatality rate
 ASPERGILLOSIS
Clinical features :
Allergic bronchopulmonary -
aspergillosis
is an allergic disease, in which the organism
colonies the mucous plugs form in the lung, but
does not invade lung tissue
is diagnosed by finding of high titer of IgE
antibodies
SYSTEMIC MYCOSES : Opportunistic
ZYGOMYCOSIS = Mucormycosis +
Phycomycosis
caused by the genera Rhizopus, Mucor &
Absidia; non-septate fungi; phylum Zygomycota;
grow repidly & predilection for invading blood
vessels & the brain

Clinical features : thoracic infectoins

occur in leukemia & lymphoma patients
abdominal-pelvic infections occurs in malnourish
patients
cutaneus infection occurs in patients withleukemia
 ZYGOMYCOSIS
Clinical features : Rhinocerebral infections
is the common form; occurs in patients with acidotic
diabetes
presents with facial swelling & blood tinged exudate in
the turbinate bones & eyes; lethargy & fixated pupil
is a fatal infections & spreads rapidly
must be diagnosed rapidly; ussually by a KOH mount of
necrotic tissue or exudate from the eye, nose, or ear

Treatment : control of diabetes; Surgical debridement;

amnphotericin B