MIKOLOGI

dr. Sigit Setyawan, M.Sc

MIKOLOGI KEDOKTERAN
• ILMU YANG MEMPELAJARI PENYAKIT-PENYAKIT PADA MANUSIA YANG
DISEBABKAN OLEH FUNGUS SERTA FUNGUS PENYEBABNYA
FUNGUS DAPAT MENYEBABKAN:
1. ALERGI
2. MISETISMUS
3. MIKOTOKSIKOSIS
4. INFEKSI / MIKOSIS
ALERGI oleh karena FUNGUS
• REAKSI HIPERSENSITIF TERHADAP FUNGUS/KOMPONEN FUNGUS
• MANIFESTASI :
* ASMA
* REAKSI ‘ID
MISETISMUS
• DISEBABKAN KARENA MASUKNYA FUNGUS BERACUN KE DALAM
TUBUH
• BERDASAR GEJALA KLINIS YANG MENONJOL, DIKENAL :
1. MISETISMUS GASTRO INTESTINALIS
2. MISETISMUS KOLERIFORMIS
3. MISETISMUS SANGUINARIUS
4. MISETISMUS NERVOSA
5. MISETISMUS SEREBRALIS
MIKOTOKSIKOSIS
• PENYAKIT OLEH KARENA MASUKNYA MIKOTOKSIN KE DALAM TUBUH
• MIKOTOKSIN :
RACUN HASIL PEMBONGKARAN SUBSTRAT TERTENTU OLEH FUNGUS
DALAM KONDISI TERTENTU
CONTOH : AFLATOKSIN -> HEPATOMA
DIBENTUK ASPERGILLUS, PENICILLIUM,
RHIZOPUS, MUCOR
MIKOSIS
• PENYAKIT OLEH KARENA INVASI FUNGUS KE DALAM JARINGAN
TUBUH MANUSIA (ATAU HEWAN); DI DALAM JARINGAN TUBUH
FUNGUS TUMBUH DAN BERKEMBANG BIAK
MISETISMUS GASTROINTESTINALIS
• BIASANYA RINGAN, GEJALA TIMBUL ½ - 2 JAM SETELAH
MENGKONSUMSI CENDAWAN
• GEJALA : MUAL, MUNTAH, DIARE BERKURANG DALAM 3 -4 JAM
• PENGOBATAN : SIMTOMATIK
MISETISMUS KOLERIFORMIS
• GEJALA PRODROMAL : 6 – 24 JAM
• TERUTAMA GEJALA GASTROINTESTINAL BERAT : SAKIT PERUT, MUAL,
MUNTAH-2 HEBAT, DIARE HEBAT SEPERTI KOLERA-> DEHIDRASI
• PUSING, KEJANG OTOT, GANGGUAN SISTEM SYARAF
• KERUSAKAN ORGAN : HATI, GINJAL & SYARAF
• PENANGANAN : ATASI KRISIS, PERBAIKI K.U., BELUM ADA
ANTIDOTUM MEMUASKAN; USAHA KELUARKAN RACUN -> TIDAK
BERGUNA
MISETISMUS NERVOSA
• Penyebab : cendawan mengandung muskarin
• Gejala muncul 15’ – 30’ sesudah mengkonsumsi cendawan
• Trias : perspirasi, salivasi, lakrimasi  mual, muntah, diare, aritmia,
miosis,sesak nafas seperti asma
• Dapat terjadi kematian (jarang)
• Penanganan : usahakan muntah, atropin sulfas 0,5 – 1 mg sub kutan,
koreksi dehidrasi
RESPON IMUN TERHADAP JAMUR
• Infeksi jamur pada manusia lebih sulit ditangani dibandingkan dengan
infeksi bakteri. eukariotik vs prokariotik
• Respon imun tubuh terhadap jamur terdiri atas respon alamiah dan juga
adaptif.
• Infeksi Aspergilus pada host diawali dengan inhalasi konidia Aspergillus dan
internalisasi ke dalam sel host.
• Sebagian besar konidia yang masuk dalam saluran nafas bagian atas dapat
dieliminasi oleh gerakan silia epitel pseudokolumner kompleks.
• Respon untuk menghindari sistem eliminasi oleh host terjadi melalui
produksi protein tertentu.
• A. fumigatus mampu mensintesis protein gliotoksin, fumagillin, serta asam
helvoik yang mampu menghambat pergerakan silia, serta memfasilitasi
proses internalisasi konidia pada sel endotel dan sel epitel.
MEKANISME JAMUR DALAM
MENGHINDARI SISTEM IMUN TUBUH
• Menghindari pengenalan struktur PAMPs yang menginduksi respon
inflamasi
• Modulasi sinyal inflamasi
• Pembentukan molekul pengumpan pada permukaan sel jamur
(Shedding of decoy conents)
• Menghindar dari respon fagositosis
• Kemampuan bertahan dengan cara membentuk morfologi yang
baru (persistence despite adversity).
• Evasi komplemen.
 TRUE SYSTEMIC (ENDEMIC) MYCOSES
• Coccidioidomycosis
• Histoplasmosis
• Blastomycosis
• Paracoccidioidomycosis
TRUE SYSTEMIC MYCOSES
General features
• Causative agents: thermally dimorphic fungi that exist in
nature, soil
• Geographic distribution varies
• Inhalation pulmonary inf.  dissemination
• No evidence of transmission among humans or animals
• Otherwise healthy individuals are infected
COCCIDIOIDOMYCOSIS
Etio: Coccidioides immitis
Micr.: Tissue (37°C): Spherules filled
with endospores
25°C: hyphae, barrel-shaped
arthroconidia
COCCIDIOIDOMYCOSIS
Pathogenesis
• Inhalation of the infectious particle, arthroconidia and
spherule formation in vivo
• Engulfment within phagosomes by alveolar MQs
• Activation of macrophages ---phagosome-lysosome fusion
---killing
• Immune complex formation
deposition leading to local inflammatory rx.s
immunosupression resulting from the binding of complexes to
cells bearing Fc receptors
COCCIDIOIDOMYCOSIS
Clinical findings
PRIMARY INF.
Asymptomatic in most
Fever, chest pain, cough, weight loss
Nodular lesions in lungs
SECONDARY (DISSEMINATED) INF. (1%)
Chronic / fulminant
Infection of lungs, meninges, bones and skin
COCCIDIOIDOMYCOSIS
Diagnosis-I
Samples: Sputum, tissue
1. Direct examination (KOH; H&E)
Spherule
2. Culture
SDA: Mould colonies at 25 °C
Spherule production in vitro by
incubation in an enriched medium at
40°C, 20% CO2
COCCIDIOIDOMYCOSIS
Diagnosis-II
3. Serology
Tube precipitin (IgM) test
Complement fixation

Skin test (coccidioidin and spheruline antigens) Negative

result may rule out the diagnosis
COCCIDIOIDOMYCOSIS
Treatment
Symptomatic treatment only (primary
infection)

• Amphotericin B
• Itraconazole
• Fluconazole(particularly for meningitis)
HISTOPLASMOSIS
• Etio: Histoplasma capsulatum
• Natural reservoir: soil, bat and avian habitats
• Location: May be prevalent all over the world, but the
incidence varies widely (most endemic in Ohio,
Mississipi, Kentucky)
• Micr. Yeast cell in tissue (37°C)
Hyphae, microconidia and
macroconidia (tuberculate
chlamydospore) at 25 °C
HISTOPLASMOSIS
Pathogenesis
• Inhalation of microconidia / primary cutaneous inoculation
• Conversion to budding yeast cells
• Phagocytosis by alveolar macrophages
• Restriction of growth or dissemination to RES by bloodstream
• Supression of cell-mediated immunity
HISTOPLASMOSIS
Clinical findings
PULMONARY INF.
Asymptomatic (%95) / mild / moderate /
severe/ chronic cavitary
DISSEMINATED INF.
RES (liver, spleen, lymph nodes, bone marrow),
mucocutaneous inf.
PRIMARY CUTANEOUS INF.
Aspergillosis and Phycomycosis

Lung infarct (left), aspergilloma (right). Diseases initiated by spores entering

the lungs.
 Aspergillosis and Phycomycosis

(top left) Young Rhizopus showing

coenocytic hyphae and spore sacs
(infectious particles). (top right) mature
Rhizopus releasing spores capable of lung
entry. (lower right) Aspergillus with
infectious spores (3-6 microns).
HISTOPLASMOSIS
Diagnosis-I
Samples: Sputum, tissue, bone marrow, CSF, blood
1. Direct examination: Giemsa / Wright
Intra- and extracellular yeast cells
2. Culture: Mould at 25°C
Conversion to yeast on an
enriched medium at 37°C
HISTOPLASMOSIS
Diagnosis-II

3. Serology: Complement fixation...

Skin test (Histoplasmin antigen):

Limited diagnostic value
 AFRICAN HISTOPLASMOSIS
Etio: Histoplasma capsulatum var. duboisii

Differentiation from classical histoplasmosis

• Larger, thick-walled yeast cells
• Pronounced giant cell formation in infected tissue
• Diminished pulmonary involvement
• Greater frequency of skin and bone lesions
HISTOPLASMOSIS
Treatment
Not required for several cases

• Amphotericin B
• Itraconazole
• Surgical resection of pulmonary lesions
BLASTOMYCOSIS

• Etio: Blastomyces dermatitidis

• Location: America, Africa, Asia
• Micr.: Yeasts at 37°C--bud is
attached to the parent cell by a
broad base
Hyphae and conidia at 25 °C
BLASTOMYCOSIS
Pathogenesis
• Inhalation of infectious particles
• Primary cutaneous inoculation
• Infiltration of macrophages and neutrophils and granuloma formation
• Oxidative killing mechanisms of neutrophils and fungicidal activity of
macrophages
BLASTOMYCOSIS
Clinical findings
ASYMPTOMATIC INF.
PULMONARY INF.
CHRONIC CUTANEOUS INF.
Subcutaneous nodule, ulceration
DISSEMINATED INF.
Skin, bone, GUT, CNS, spleen
PRIMARY CUTANEOUS INF.
BLASTOMYCOSIS
Diagnosis-I
Samples: Sputum, tissue
1. Direct micr.ic exam: KOH, H&E
Yeast cells; bud is attached to the
parent cell by a broad base

2. Culture: Mould at 25°C

Conversion to yeast on an
enriched medium at 37°C
 BLASTOMYCOSIS
Diagnosis-II
3. Serology: Immunodiffusion test
ELISA to detect antibodies to
exoantigen A

Skin test (Blastomycin antigen)

Limited/no diagnostic value
BLASTOMYCOSIS
Treatment

• Amphotericin B
• Itraconazole
• Fluconazole
• Corrective surgery
PARACOCCIDIOIDOMYCOSIS
• Etio: Paracoccidioides brasiliensis
• Location: Central and South America
• Pathogenesis: Inhalation of conidia
*The inf. is more common in males
• Micr.: At 37°C (in tissue ): multiply
budding yeasts; the buds are attached
to the parent cell by a narrow base
At 25 °C: hyphae and conidia
 PARACOCCIDIOIDOMYCOSIS
Determinants of pathogenicity
• The fungus has a protein in its cytoplasm which binds only to estrogen
but not to testosterone; this binding prevents conversion to yeast form
at 37°C.
• Yeast cell wall polysaccharides (alpha-glucan) stimulate granuloma
formation.
PARACOCCIDIOIDOMYCOSIS
Clinical findings
• ASYMPTOMATIC INF.
• LATENT FORM (duration variable)
• SYMPTOMATIC INF.
Noduler lesions in lungs
Dissemination to other organs (rare)
Cryptococcosis

PAS stain showing encapsulated yeast in

tissue

Pulmonary cryptococcosis
 PARACOCCIDIOIDOMYCOSIS
Diagnosis-I
Samples: Sputum, tissue
1. Direct micr.ic exam.: KOH, H&E
multiply budding yeasts; the
buds are attached to the
parent cell by a narrow base
2. Culture: Mould at 25°C
Conversion to yeast on an
enriched medium at 37°C
PARACOCCIDIOIDOMYCOSIS
Diagnosis-II

3. Serology: Immunodiffusion
Complement fixation
PARACOCCIDIOIDOMYCOSIS
Treatment
• Amphotericin B
• Ketoconazole
• Itraconazole
• Sulfonamides
Endogenously acquired Candidiasis

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.