Pepy Dwi Endraswari, dr. INFEKSI FUNGI

Mikroba eukariot: Fungi Algae Protozoa Parasitic helminths

Peran fungi decomposer Sumber antibiotik Membantu proses pembuatan makanan Efek negatif: mycoses, produksi toxin, merusak makanan

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.

Penyakit yang ditimbulkan oleh infeksi fungi:

Penyakit yang ditimbulkan oleh infeksi fungi:

Pokok Bahasan Karakteristik fungi Epidemiologi Klasifikasi 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

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

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

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.

Asexual mold spores

4 main divisions based on spore type Zygomycota (Conjugation Fungi) Ascomycota (Sac Fungi) Basidiomycota (Club Fungi) Deuteromycota – no sexual spores

I. Zygospores: Also known as bread molds.

II. Ascospores

III. Basidospores

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

INFEKSI JAMUR (Mycoses) Jamur Penyebab Epidemiologi Manifestasi klinik Diagnosis Mikrobiologi Terapi

Mycoses Merupakan infeksi kronis, karena pertumbuhan jamur yang lambat Klasifikasi: 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 Chromoblastomycosisi Sporothricosis Mycetoma Phaeohypomycois Aspergillosis Blastomycosis Candidosis Coccidioidomycosis Histoplasmosis Cryptococcosis Geothrichosis Paracoccidioidomycosis Zygomycosis Fusariosis Trichosporonsis Geothricosis 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 e.g. Epidermophyton floccosum, Microsporum audouinii, M. ferrugineum and several Trichophyton spp.

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.

Mode and vehicle of transmission: 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. Penicillium, one of numerous soil fungi causing this disease. Patient

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 Incidence Clinical Manifestation Pityriasis versicolor Malassezia furfur  Common Hipopigmented macule Tinea nigra Exophiala werneckii     Rare black macules White piedra Trichosporon beigelii black nodule on hair shaft  Black piedra Piedraia hortae   creme-colored nodules on hair shaft

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.

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 barbae Tinea corporis Tinea Unguinum

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

Skin scrapping: hiphae Microscopic & Culture Skin scrapping: hiphae Exothrix: spore Endothrix: spore Culture on SDA

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 Incidence Clinical manifestation Sporotrichosis Sporothrix schenckii  Rare Nodules and ulcers along lymphatics at site of inoculation Chromoblastomycosis  Fonsecaea, Phialophora,  Cladosporium etc. Warty nodules that progress to "cauliflower-like" appearance at site of inoculation  Mycotic mycetoma Pseudallescheria, Madurella,  Acremonium, Exophiala etc. Draining sinus tracts at site of inoculation

Subcutaneus mycoses: SPOROTRICHOSIS Sinonim: Rose Garnener’s disease Manifestasi klinis Cutaneus sporotrichosis Infeksi sistemik

Pewarnaan GMS pada spesimen biopsi 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.

*more common in endemic areas. 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  Blastomycosis Blastomyces dermatitidis   Paracoccidioidomycosis Paracoccidioides brasiliensis   Sporotrichosis Sporothrix schenkii Rare Penicilliosis marnefffei Penicillium marneffei *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. Pneumocystosis Pneumocystis carinii

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 Oropharyngeal candidiasis: including thrush, glossitis, stomatitis and angular cheilitis (perleche). Cutaneous candidiasis: including intertrigo, diaper candidiasis, paronychia and onychomycosis. Neonatal and congenital candidiasis: Vulvovaginal candidiasis and balanitis: 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

Avoid contact with Birds 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

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