Transcript Opportunistic Fungal Infections.

Pepy Dwi Endraswari, dr.
INFEKSI FUNGI
Mikroba eukariot:
 Fungi
 Algae
 Protozoa
 Parasitic helminths
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Peran fungi
 decomposer
 Sumber antibiotik
 Membantu proses pembuatan makanan
 Efek negatif: mycoses, produksi toxin, merusak
makanan
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Kingdom Fungi
 Terdiri dari >100,000 species dibagi menjadi 2
groups:
 macroscopic fungi ( mushrooms)
 microscopic fungi (molds, yeasts)
 Dari >1oo,000 species yang ditemukan  ± 100
spesies patogen bagi manusia.
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Penyakit yang ditimbulkan oleh infeksi
fungi:
Penyakit yang ditimbulkan oleh infeksi
fungi:
Pokok Bahasan
 Karakteristik fungi
 Morfologi
 Reproduksi
 Nutrisi
 Epidemiologi
 Klasifikasi Fungi
 Infeksi Fungi  mycoses
1. Morfologi Fungi
 Dinding sel: mengandung chitin
 Membran sel: mengandung ergosterol
 Mikroskopik: memiliki 2 macam morfologi:
 yeast – berbentuk bulat-oval
 hyphae – berbentuk filamen , disebut
juga:molds
 Beberapa fungi mempunyai kedua fase
tersebut  disebut sbg fungi dimorphic
merupakan karakteristik jamur patogen
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Yeast
Unicellular fungi, nonfilamentous, typically
oval or spherical cells. Reproduce by
mitosis.
Yeasts are facultative anaerobes, which
allows them to grow in a variety of
environments.
 When oxygen is available, they carry out aerobic respiration.
 When oxygen is not available, they ferment carbohydrates to produce
ethanol and carbon dioxide.
Morfologi
yeast
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Hyphae / Molds
 Multicellular, filamentous fungi (Long filaments of cells
joined together)
 Identified by physical appearance, colony
characteristics, and reproductive spores.
 Hiphae:
 Septate hyphae: Cells are divided by cross-walls (septa).
 Coenocytic (Aseptate) hyphae: Long, continuous cells that are
not divided by septa.
 Part of hiphae:
 Vegetative Hypha: Portion that obtains nutrients.
 Reproductive or Aerial Hypha: Portion connected with
reproduction.
 Mycelium: Large, visible, filamentous mass made up of
many hyphae.
Morfologi hiphae/molds
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Morfologi Hiphae / Molds
Mycelium: Large, Visible Mass of Hyphae
Dimorphic Fungi
Can exist as both multicellular fungi (molds) and
yeasts.
Many pathogenic species.
 Mold form produces aerial and vegetative hyphae.
 Yeast form reproduces by budding.
Dimorphism in pathogenic fungi typically depends
on temperature:
 At 37oC: Yeast form.
 At 25oC: Mold form.
Dimorphism in nonpathogenic fungi may depend
on other factors: Carbon dioxide concentration
2. Reproduksi Fungi
 Hiphae : form spores
 asexual reproduction – spores are formed through
budding or in conidia or sporangiospores
 sexual reproduction – spores are formed following
fusion of male & female strains & formation of sexual
structure
 Yeast : Asexual reproduction by mitosis
 Fission yeasts: Divide evenly to produce two new cells
 Budding yeasts: Divide unevenly by budding
Budding yeasts can form pseudohypha, a short chain of undetached
cells.
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Asexual mold spores
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4 main divisions based on spore
type
1. Zygomycota (Conjugation Fungi)
2. Ascomycota (Sac Fungi)
3. Basidiomycota (Club Fungi)
4. Deuteromycota – no sexual spores
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I. Zygospores: Also known as
bread molds.
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II. Ascospores
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III. Basidospores
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Nutrisi Fungi
 heterotrophic
 Mayoritas tidak membahayakan, hidup secara
saprofit pada tumbuhan atau hewan yang mati
 Beberapa mrpkn parasit yang hidup pada jaringan
organisme lain  infeksi jamur mycoses
 growth temperature 20o-40oC
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INFEKSI JAMUR
(Mycoses)
Jamur Penyebab
Epidemiologi
Manifestasi klinik
Diagnosis
Mikrobiologi
Terapi
Mycoses
 Merupakan infeksi kronis, karena
pertumbuhan jamur yang lambat
 Klasifikasi:
1.
2.
3.
4.
5.
Superficial mycoses
Cutaneus mycoses
Subcutaneus mycoses
Systemic mycoses
Opportunistic mycoses
General Clinical Classification
of Pathogenic Fungi
Superficial
Cutaneus
Subcutaneus Sistemic
Opportonistic
•Pityriasis
versicolor
•Tinea niegra
•Piedra
•Tinea pedis
•Tinea
unguinum
•Tinea corporis
•Tinea cruris
•Tinea manus
•Tinea capitis
•Tinea barbae
•Chromoblasto
mycosisi
•Sporothricosis
•Mycetoma
•Phaeohypom
ycois
•Aspergillosis
•Candidosis
•Cryptococcosis
•Zygomycosis
•Aspergillosis
•Blastomycosis
•Candidosis
•Coccidioidomyc
osis
•Histoplasmosis
•Cryptococcosis
•Geothrichosis
•Paracoccidioido
mycosis
•Zygomycosis
•Fusariosis
•Trichosporonsis
•Geothricosis
•Fusariosis
•Trichosporonosis
•Others
EPIDEMIOLOGI
How can you control a disease if
you don’t know the source?
Factors to consider:
- Where do pathogens live in nature?
- How do they disseminate?
- What is the human portal of entry?
- Why is a human susceptible?
Epidemiologically we have three groups of
fungi:
1.) Dermatophytoses: man, animal, soil.
2.) Exogenously acquired: soil, air.
3.) Endogenous in origin: normal flora.
Let’s look at the above three groups separately
Three groups (con’t)
1.) Dermatophytoses:
Dermatophytoses (con’t)
Fungi which caused ringworms
These diseases are classified by the mode
transmission:
a.) Anthropophilic implies organisms that are
spread from man to man
Epidermophyton floccosum,
Microsporum
audouinii, M. ferrugineum and several Trichophyton spp.
e.g.
Dermatophytoses (con’t)
b.) Geophilic are organisms that live in soil and
maybe transmitted to man by soil contact, e.g.
Microsporum gypseum (often causing tinea
barbae).
c.) Zoophilic are organisms which are transmitted
to man from animals other than man (dogs, cats,
cattle, etc.). Some zoophilic dermatophytes are
Microsporum canis, Trichophyton verrucosum and
two varieties of T. mentagrophytes.
Dermatophytoses (con’t)
Mode and vehicle of transmission:
- Transmitted by contact with soil, infected
humans and infected animals.
- Transmission is with hyphae and/or spores in
soil or infected skin, nails or hair.
- In some cases fomite transmission is with
infected clothing.
2.)
Exogenously acquired: soil & air
 This includes all other mycoses (one major
exception: Opportunistic infection by candida
albicans).
Disease is acquired from one of two sources:
A.) Soil
Where fungi live forming hyphae and spores, they
enter the host via punctured wounds and trauma.
Spore size is not important. The following are
some examples of diseases that are acquired by
this mechanism.Example: Subcutaneus mycosis
(Sporothricosis, Mycetoma, Chromomycosis) , Mycotic
keratitis
Exogenously acquired:Subcutaneus
mycoses
Exogenously acquired:Sporotrichosis
Note hyphae and spores which live in
nature on plant material and are the
infectious particles.
This is the pathogenic phase which is
not infectious. It can be grown in
the laboratory at 35 C, i.e. the
fungus is
dimorphic
Exogenously acquired:Mycotic
Keratitis
- Numerous fungi cause keratitis worldwide but mostly in tropical
or heavily agricultural areas. Spores and hyphae are implanted
onto eye following trauma.
Patient
Penicillium, one of numerous soil
fungi causing this disease.
B.) Air and lungs
These are fungi which grow in nature but produce airborne
infectious particles which have the correct size limitations to
enter the human lung.
Note that airborne particles greater than 6 microns cannot
enter the human lung.
Air and lungs (con’t)
•Aspergillosis  Organisms in environment, cannot eliminate
•Histoplasmosis Spread from bird droppings, especially
blackbirds, chickens and bats
•Cryptococcosis In pigeon droppings and near Eucalyptus
trees
•Coccidioidomycosis in area characterized by little rainfall and
intense heat. Some evidence that the organism Coccidioides
immitis favors salty soils.
•SporothricosisThe pulmonary form is caused by spores
entering the lungs from peat moss or other dusty forms of
organic matter.
Air and lung: Aspergillosis
Lung infarct (left), aspergilloma (right). Diseases initiated by spores
entering the lungs.
Aspergillus with infectious spores
(3-6 microns).
3.) Endogenously acquired
Candidiasis is the only major systemic mycosis that
is endogenous in origin. That means that the
numerous yeast species are part of mans’ normal
flora. This means that the key to infection is
predisposing factors,
e.g. 90 % of AIDS patients have candidiasis.
The only exception to being endogenous in origin is
STD candidiasis and nosocomial acquired
candidiasis, usually from hospital workers.
Today, candidiasis is the most important systemic
mycoses in the world.
Candidiasis (con’t)
Dissemination or disease spread is with yeast cells and/or hyphae. The
hyphae looks distorted, thus it is sometimes called “pseudohyphae”.
The disease is worldwide and fatal in susceptible hosts.
Yeast cells and pseudohyphae seen in patients.
Conclusions
1.) Most systemic mycoses are acquired from fungi which live
in soil on decaying vegetation.
2.) Fungi produce hyphae and spores which enter humans via
a punctured wound or, if less than 6 microns, can enter the
lungs.
3.) Dermatophytoses (ringworms) can be transmitted to man
from soil, animals and other men.
4.) Candidiasis is the only major mycosis that is endogenous in
origin.
5.) Most systemic mycoses are seen in patients that have
depressed immunity. This may be genetic or acquired.
CLINICAL MYCOLOGY
1. Superficial Mycoses
 Infections of hair shafts and superficial
epidermal cells.
 Prevalent in tropical climates.
1. Superficial mycosis
Definition: Infections of hair shafts and superficial
epidermal cells. Limited to the stratum corneum. No
Inflamation. Cosmetic problem.
Disease
Causative
organisms
Pityriasis
versicolor
Malassezia
furfur
Tinea nigra
Exophiala
werneckii
Rare
White piedra
Trichosporon
beigelii
Common
black nodule on
hair shaft
Rare
creme-colored
nodules on hair
shaft
Black piedra
Piedraia hortae
Incidence
Clinical
Manifestation
Common
Hipopigmented
macule
black macules
Clinical Manifestation
Diagnosis laboratorium
 Spesimen: skin scrapping (kerokan kulit),
potongan rambut  pengecatan dengan
KOH 10-20%  diamati dibawah mikroskop
 Terapi: obat antifungal topikal
2. Cutaneus Mycoses
 Infeksi jamur pada jaringan
berkeratin (kulit, rambut dan
kuku)
 Jamur mensekresi keratinase, suatu enzym
yang mendegradasi keratin.
 Infeksi ditransmisikan melalui kontak
langsung dengan kulit, kuku atau rambut
yang terinfeksi.
Cutaneus mycoses
Disease
Causative organisms
Incidence
Dermatophytosis
Ringworm of the scalp,
glabrous skin and nails.
Dermatophytes
(Microsporum,
Trichophyton,
Epidermophyton)
Common
Candidiasis of skin and
and nails.
Candida albicans
and related species.
Common
Dermatophytosis: Ringworm of the
scalp, glabrous skin and nails
Disease
Symptoms
Tinea capitis
ringworm lesion of scalp
Tinea corporis
ringworm lesion of trunk, arms, legs
Tinea manus
ringworm lesion of hand
Tinea cruris "jock itch"
ringworm lesion of groin
Tinea pedis"athlete's foot"
ringworm lesion of foot
Tinea unguium
infection of nails
Ectothrix
infection of hair shaft surface
Endothrix
infection of hair shaft interior
Dermatophytosis: Clinical
Manifestation
Tinea Pedis: is transmitted
via the feet by
desquamated skin scales in
substrates like carpet and
matting
Dermatophytosis: Clinical
Manifestation
Tinea cruris
Tinea Unguinum
Tinea barbae
Tinea corporis
Dermatophytosis: Clinical Manifestation
Tinea Capitis: Exothrix, Endothrix, Favus
"Kerion" lesion caused by T. verrucosum
following contact with cattle.
Tinea capitis showing extensive
hair loss caused by M. canis.
Endothrix tinea capitis (left) caused by T. tonsurans and "black dot" tinea capitis
(right) caused by T. violaceum
Dermatophytosis:
Laboratoy Diagnosis
 Spesimen: Skin Scrapings, nail scrapings and
epilated hairs
 Method:
 Direct Microscopy: KOH 10-20% and ink parker
 Culture: Sabouraud's dextrose agar containing
cycloheximide incubated at 26-28C for 4 weeks
Microscopic & Culture
Skin scrapping:
hiphae
Exothrix: spore
Culture on SDA
Endothrix: spore
3. Subcutaneus Mycoses
 Infeksi jamur pada jaringan subkutan.
 Disebabkan oleh jamur saprofit yang hidup
pada tanah atau tanaman.
 Infeksi terjadi karena masuknya spora atau
micelium pada luka kulit.
 Dapat menyebar melalui pembuluh limfe.
3. Subcutaneus Mycoses
Disease
Causative
organisms
Incide
nce
Sporotrichosis
Sporothrix
schenckii
Rare
Nodules and ulcers along
lymphatics at site of inoculation
Chromoblastomycosis
Fonsecaea,
Phialophora,
Cladosporium etc.
Rare
Warty nodules that progress to
"cauliflower-like" appearance at
site of inoculation
Mycotic mycetoma
Pseudallescheria,
Madurella,
Acremonium,
Exophiala etc.
Rare
Clinical manifestation
Draining sinus tracts at site of
inoculation
Subcutaneus mycoses:
SPOROTRICHOSIS
 Sinonim: Rose Garnener’s disease
 Manifestasi klinis
Cutaneus sporotrichosis
Infeksi sistemik
Sporotrichosis
Characteristic
lymphadenopathy.
Pewarnaan GMS pada
spesimen biopsi
Subcutaneus mycoses:
Chromoblastomycosis
 Penyebab: Fonsecaea pedrosoi, Fonsecaea
compacta, Phialophora verrucosa,
Cladosporium carrionii
 Manifestasi klinik:
 Nodule verrucous atau plaque
 Sering terjadi di daerah tropis yang lembab
 Kebanyakan pada kaki, didahului dgn luka ( bisa
pada bagian tubuh lain)
 Walaupun jarang, dapat menyerang otak
(menyebar secra hematogen)
Chromomycosis
Etiologic agent showing dematiaceous
hyphae and spores
10-year old case
Subcutaneus mycoses:
MYCETOMA
 Sinonim: Madura foot
 Penyebab:
 Jamur (Eumycotic mycetoma)
 Kuman yang mirip jamur (Actinomycotic mycetoma)
 Gx klinis:
 infeksi subkutan yang membengkak seperti tumor dan
adanya sinus yang mengeluarkan nanah dan granul / grains
seperti butiran pasir yang mengandung kuman
 Ditemukannya granule/grains sangat penting untuk
diagnosa
 bbrp jamur/bakteri penyebab mycetoma dapat di isolasi
dari tanah/ pohon.
Mycetomas
15-year old case of mycetoma
One of many etiologic agents .Note
hyphae and spores which live in
nature. Fusarium sp.
4. Systemic Mycoses

Menginfeksi jaringan/organ secara sistemik

Biasanya disebabkan jamur yang hidup di tanah.
Disease
Causative organisms
Incidence
Histoplasmosis
Histoplasma capsulatum
Histoplasma dubosii
Rare*
Coccidioidomycosis
Coccidioides immitis
Rare*
Blastomycosis
Blastomyces dermatitidis
Rare*
Paracoccidioidomycosis
Paracoccidioides
brasiliensis
Rare*
Sporotrichosis
Sporothrix schenkii
Rare
Penicilliosis marnefffei
Penicillium marneffei
Rare*
*more common in endemic areas.
Histoplasmosis
 intracellular infection of the reticuloendothelial




system
caused by the inhalation of conidia from
Histoplasma capsulatum
Isolation:soil enriched with excreta from
chicken, starlings (burung jalak) and bats
(kelelawar).
Major endemic: River Valley in the U.S.A.
Two varieties of H. capsulatum: var. capsulatum
(common) and var. duboisii
HISTOPLASSMOSIS
 Clinical manifestations:
 95% of cases of histoplasmosis are
inapparent, subclinical or benign.
 Five percent of the cases have chronic
progressive lung disease, chronic cutaneous
or systemic disease or an acute fulminating
fatal systemic disease.
 All stages of this disease may mimic
tuberculosis.
Histoplasmosis
COCCIDIOIDOMYCOSIS
initially:a respiratory infection, resulting from
the inhalation of conidia,
resolves rapidly leaving the patient with a
strong specific immunity
in some individuals the disease may progress.
Coccidioidomycosis (con’t)
Coccidioides immitis is a soil inhabiting
fungus endemic in south-western U.S.A.,
northern Mexico and various centres in
South America. Several cases have now
been diagnosed in Australia, all in patients
with a history of travel to endemic areas.
The organism Coccidioides immitis is found
in desert soils as shown here. The spores
are < 7 microns, become airborne, enter the
lungs and initiate disease.
fever, pleuritic chest pain, cough, malaise, headache,
myalgia, night sweats and loss of appetite. Many
patients also develop a mild, diffuse erythematous or
maculopapular rash on the trunk and limbs.
5-10% of patients that do develop symptoms are left with
pulmonary residual nodule or cavity that is usually
detected several months or years later.
5% of patients may develop metapulmonary dissemination
to the meninges, bones, joints and subcutaneous and
cutaneous tissues, within the first few weeks to months
after the onset of primary infection .
5. Opportunistic Mycoses
 Adalah infeksi yang terjadi pada manusia/hewan dengan sistem
pertahanan tubuh yang menurun :

pasien AIDS, pasien kanker

Individu yg mendapat terapi antibiotik spektrum luas

neonatus / individu yang sangat tua
 Diabetes melitus
 Resipien organ transplan
 Terapi steroid
 Pada sistem imun yang baik tidak menyebabkan penyakit.
 Penyebab: Flora normal ataupun fungi yang ada di lingkungan
5. Opportunistic Infection
Disease
Causative organisms
Incidence
Candidiasis
Candida albicans and
related species.
Common
Cryptococcosis
Cryptococcus neoformans
Rare/Common
Aspergillosis
Aspergillus fumigatus etc.
Rare
Zygomycosis
(Mucormycosis)
Rhizopus, Mucor,
Rhizomucor,
Absidia etc.
Rare
Pneumocystosis
Pneumocystis carinii
Rare
Opportunistic mycoses:
Candidiasis
 Candidiasis also called as Monoliasis,
 Can infect Skin, Mucosa, or Internal Organs
 Normal flora
Exist in Mouth, Gastrointestinal tract, Vagina, skin in 20 %
of normal Individuals.
 Colonization increases with age,in pregnancy,
Hospitalization
 Important etiological agent presenting as opportunistic
infection in Diabetus and HIV patients
Clinical Manifestation
1. Oropharyngeal candidiasis: including thrush, glossitis, stomatitis and angular
cheilitis (perleche).
2. Cutaneous candidiasis: including intertrigo, diaper candidiasis, paronychia and
onychomycosis.
3. Neonatal and congenital candidiasis:
4. Vulvovaginal candidiasis and balanitis:
5. Candidemia (Candida septicemia) and disseminated candidiasis,etc.
Laboratory diagnosis
Clinical specimen:
• Skin scrapings,
• Mucosal scrapping,
• Vaginal secretions
• Blood ans other body fluid
Method:
• Direct mikroskopic
• Cultures : on Sabouraud's Glucose agar
• PCR
CRYPTOCOCCOSIS
Morphology
A true yeast
Round 4 – 10 microns
Surrounded by Mucopolysaccharide capsule.
Negative staining with India Ink and Nigrosin
60% of the infected prove positive by India Ink
preparation on examination of CSF
Life cycle of C.neofromans
Found in wild/Domesticated birds (Pigeon) and eucalyptus
tree.Pigeons carry C.neofromans, but do not get infected.
Pathogenesis
 Enters through lungs - inhalation of
Basidiospores of C neoformans
 Enters deep into lungs.
 Self limiting in most cases,
 Pulmonary infections can occur.
 Present as discrete nodules - Cryptococcoma.
Pathogenesis
 Can infect normal humans
 Abnormalities of T lymphocyte function
aggravates the clinical manifestations (In AIDS
3- 20% develop Cryptococcosis)
 Clinical manifestation: Chronic meningitis ,
Meningo encephalitis ,head ache low grade
fever,Visual abnormalities ,Coma – fatal
 Can manifest with involvement of ,Skin,
mucosa,organs,Bones,and as Disseminated
form.
Can mimic like Tuberculosis
Laboratory Diagnosis.
 Mikroskopic: Indian ink staining, Gram staining
 Kultur
:Cultures on Sabouraud dextrose agar
 Serologis: detection of Capsular antigen
Treatment
 Immune competent - Antifungal drug
 AIDS patients are not totally cured ,
Relapses are frequent with fatal outcome.
Prevention:
Avoid contact with Birds
ASPERGILLOSIS
Aspergillosis
 In nature > 100 species of Aspergillosis exist,





Few are important as human pathogens
1 A.fumigatus
2 A.niger
3 A.flavus
4 A.terreus
5 A.nidulans
Fungal spores enters through
respiratory tract
Morphology
 Khas: hifa dengan
spora yang khas
 Conidiophores
terminates in a
swollen cell vesicle
surrounded by one or
two rows of cell (
Streigmata ) from
which chains of
asexual conidia are
produced
Pathogenesis - varied
clinical presentations
Allergic Aspergillosis – Atopic individuals, with
elevated IgE levels
10-20% of Asthmatics react to A.fumigatus
Allergic alveoitis follows particularly heavy and
repeated exposure to larger number of spores
 Maltsters Lung – causes allergic alveolitis, who handle barley on
which A.claveus has sporulated during malting process
Pathogenesis
Aspergilloma – A fungal
ball, fungus colonize
Preexisting
(Tuberculosis ) cavities
in the lung and form
compact ball of
Mycelium which is later
surrounded by dense
fibrous wall presents
with cough, sputum
production
Haemoptysis occurs
due to invasion of blood
vessels
 Invasive Aspergillosis
occurs in
immunocompromised
with underlying disease
 A.fumigatus >>
 Fungus invades blood
vessels, causes thrombosis
septic emboli
 Can spread to Kidney and
heart.
Pathogenesis