INFEKSI FUNGI

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INFEKSI FUNGI

• Pepy Dwi Endraswari, dr.

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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 gt100,000 species dibagi menjadi 2
  groups
• macroscopic fungi ( mushrooms)
• microscopic fungi (molds, yeasts)
• Dari gt1oo,000 species yang ditemukan ? 100
  spesies patogen bagi manusia.

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Penyakit yang ditimbulkan oleh infeksi fungi
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Penyakit yang ditimbulkan oleh infeksi fungi
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Pokok Bahasan

• Karakteristik fungi
• Morfologi
• Reproduksi
• Nutrisi
• Epidemiologi
• Klasifikasi Fungi
• Infeksi Fungi ? mycoses

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1. Morfologi Fungi

• Dinding sel mengandung chitin
• Membran sel mengandung ergosterol
• Mikroskopik memiliki 2 macam morfologi
• yeast berbentuk bulat-oval
• hyphae berbentuk filamen , disebut jugamolds
• 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.

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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.

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Morfologi hiphae/molds
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Morfologi Hiphae / Molds
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Mycelium Large, Visible Mass of Hyphae
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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

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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

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Mycoses

• Merupakan infeksi kronis, karena pertumbuhan
  jamur yang lambat
• Klasifikasi
• Superficial mycoses
• Cutaneus mycoses
• Subcutaneus mycoses
• Systemic mycoses
• Opportunistic mycoses

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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 Chromoblastomycosisi Sporothricosis Mycetoma Phaeohypomycois Aspergillosis Blastomycosis Candidosis Coccidioidomycosis Histoplasmosis Cryptococcosis Geothrichosis Paracoccidioidomycosis Zygomycosis Fusariosis Trichosporonsis Aspergillosis Candidosis Cryptococcosis Zygomycosis Geothricosis Fusariosis Trichosporonosis Others
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Epidemiologi
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How can you control a disease if you dont know
the source?
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• 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?

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Epidemiologically we have three groups of fungi
1.) Dermatophytoses man, animal, soil. 2.)
Exogenously acquired soil, air. 3.) Endogenous
in origin normal flora.
Lets look at the above three groups separately
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Three groups (cont) 1.) Dermatophytoses
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Dermatophytoses (cont)
?Fungi which caused ringworms These diseases are
classified by the mode transmission a.)
Anthropophilic implies organisms that are spread
from man to man e.g. Epidermophyton
floccosum, Microsporum audouinii, M.
ferrugineum and several Trichophyton spp.
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Dermatophytoses (cont)
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.
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Dermatophytoses (cont)

• 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.

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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
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Exogenously acquiredSubcutaneus mycoses
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Exogenously acquiredSporotrichosis
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
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Exogenously acquiredMycotic Keratitis -
Numerous fungi cause keratitis worldwide but
mostly in tropical or heavily agricultural areas.
Spores and hyphae are implanted onto eye
following trauma.
Penicillium, one of numerous soil fungi causing
this disease.
Patient
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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.
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Air and lungs (cont)

• 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.

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Air and lung Aspergillosis
Lung infarct (left), aspergilloma (right).
Diseases initiated by spores entering the lungs.
Aspergillus with infectious spores (3-6 microns).
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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.
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Candidiasis (cont)
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.
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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.
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Clinical Mycology
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1. Superficial Mycoses

• Infections of hair shafts and superficial
  epidermal cells.
• Prevalent in tropical climates.

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1. Superficial mycosis
Definition Infections of hair shafts and
superficial epidermal cells. Limited to the
stratum corneum. No Inflamation. Cosmetic problem.
Disease Causative organisms Incidence Clinical Manifestation
Pityriasis versicolor Malassezia furfur  Common Hipopigmented macule
Tinea nigra Exophiala werneckii     Rare black macules
White piedra Trichosporon beigelii Common black nodule on hair shaft 
Black piedra Piedraia hortae   Rare creme-colored nodules on hair shaft
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Clinical Manifestation
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Diagnosis laboratorium

• Spesimen skin scrapping (kerokan kulit),
  potongan rambut ? pengecatan dengan KOH 10-20 ?
  diamati dibawah mikroskop
• Terapi obat antifungal topikal

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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.

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Cutaneus mycoses
Disease Causative organisms   Incidence
DermatophytosisRingworm of the scalp,glabrous skin and nails. Dermatophytes (Microsporum, Trichophyton, Epidermophyton) Common
Candidiasis of skin andand nails. Candida albicans and  related species. Common
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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
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Dermatophytosis Clinical Manifestation
Tinea Pedis is transmitted via the feet by
desquamated skin scales in substrates like carpet
and matting
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Dermatophytosis Clinical Manifestation
Tinea cruris
Tinea barbae
Tinea corporis
Tinea Unguinum
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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
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DermatophytosisLaboratoy 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

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Microscopic Culture
Skin scrapping hiphae
Exothrix spore
Endothrix spore
Culture on SDA
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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.

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3. Subcutaneus Mycoses
Disease   Causative organisms Incidence Clinical manifestation
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 Draining sinus tracts at site of inoculation
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Subcutaneus mycoses SPOROTRICHOSIS

• Sinonim Rose Garneners disease
• Manifestasi klinis
• Cutaneus sporotrichosis
• Infeksi sistemik

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Sporotrichosis
Characteristic lymphadenopathy.
Pewarnaan GMS pada spesimen biopsi
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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)

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Chromomycosis
Etiologic agent showing dematiaceous hyphae and
spores
10-year old case
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Subcutaneus mycosesMYCETOMA

• 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.

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Mycetomas
15-year old case of mycetoma
One of many etiologic agents .Note hyphae and
spores which live in nature. Fusarium sp.
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4. Systemic Mycoses

• Menginfeksi jaringan/organ secara sistemik
• Biasanya disebabkan jamur yang hidup di tanah.

Disease  Causative organisms  Incidence
Histoplasmosis Histoplasma capsulatumHistoplasma 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.
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Histoplasmosis

• intracellular infection of the reticuloendothelial
  system
• caused by the inhalation of conidia from
  Histoplasma capsulatum
• Isolationsoil 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

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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.

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Histoplasmosis
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COCCIDIOIDOMYCOSIS

• initiallya 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.

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Coccidioidomycosis (cont)
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 lt 7
microns, become airborne, enter the lungs and
initiate disease.
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• 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 .

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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

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5. Opportunistic Infection
Disease Causative organisms Incidence
Candidiasis  Candida albicans andrelated species. Common
Cryptococcosis Cryptococcus neoformans  Rare/Common
Aspergillosis Aspergillus fumigatus etc.   Rare
Zygomycosis (Mucormycosis) Rhizopus, Mucor, Rhizomucor,Absidia etc. Rare
Pneumocystosis Pneumocystis carinii Rare
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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

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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.

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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

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Cryptococcosis
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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

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Life cycle of C.neofromans
Found in wild/Domesticated birds (Pigeon) and
eucalyptus tree.Pigeons carry C.neofromans, but
do not get infected.
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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.

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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

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Laboratory Diagnosis.

• Mikroskopic Indian ink staining, Gram staining
• Kultur Cultures on Sabouraud dextrose agar
• Serologis detection of Capsular antigen

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Treatment

• Immune competent - Antifungal drug
• AIDS patients are not totally cured , Relapses
  are frequent with fatal outcome.
• Prevention
• Avoid contact with Birds

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ASPERGILLOSIS
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Aspergillosis

• In nature gt 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

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Fungal spores enters through respiratory tract
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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

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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

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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

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Pathogenesis

• Invasive Aspergillosis
• occurs in immunocompromised with
  underlying disease
• A.fumigatus gtgt
• Fungus invades blood vessels, causes thrombosis
  septic emboli
• Can spread to Kidney and heart.