3Peran fungi decomposer Sumber antibiotik Membantu proses pembuatan makananEfek negatif: mycoses, produksi toxin, merusak makanan
4Kingdom FungiTerdiri 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.
81. Morfologi Fungi Dinding sel: mengandung chitin Membran sel: mengandung ergosterolMikroskopik: memiliki 2 macam morfologi:yeast – berbentuk bulat-ovalhyphae – berbentuk filamen , disebut juga:moldsBeberapa fungi mempunyai kedua fase tersebut disebut sbg fungi dimorphic merupakan karakteristik jamur patogen
9YeastUnicellular 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.
11Hyphae / MoldsMulticellular, 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.
15Dimorphic FungiCan 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
162. Reproduksi Fungi Hiphae : form spores asexual reproduction – spores are formed through budding or in conidia or sporangiosporessexual reproduction – spores are formed following fusion of male & female strains & formation of sexual structureYeast : Asexual reproduction by mitosisFission yeasts: Divide evenly to produce two new cellsBudding yeasts: Divide unevenly by buddingBudding yeasts can form pseudohypha, a short chain of undetached cells.
22Nutrisi Fungi heterotrophic Mayoritas tidak membahayakan, hidup secara saprofit pada tumbuhan atau hewan yang matiBeberapa mrpkn parasit yang hidup pada jaringan organisme lain infeksi jamur mycosesgrowth temperature 20o-40oC
27How can you control a disease if you don’t know the source?
28Factors to consider: - Where do pathogens live in nature? How do they disseminate?What is the human portal of entry?Why is a human susceptible?
29Epidemiologically 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
31Dermatophytoses (con’t) Fungi which caused ringwormsThese diseases are classified by the mode transmission:a.) Anthropophilic implies organisms that are spread from man to mane.g. Epidermophyton floccosum, Microsporum audouinii, M. ferrugineum and several Trichophyton spp.
32Dermatophytoses (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.
33Mode 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.
342.) 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.) SoilWhere 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
36Exogenously 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
37Exogenously 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
38B.) Air and lungsThese 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.
39Air and lungs (con’t)Aspergillosis Organisms in environment, cannot eliminateHistoplasmosis Spread from bird droppings, especially blackbirds, chickens and batsCryptococcosis In pigeon droppings and near Eucalyptus treesCoccidioidomycosis in area characterized by little rainfall and intense heat. Some evidence that the organism Coccidioides immitis favors salty soils.SporothricosisThe pulmonary form is caused by spores entering the lungs from peat moss or other dusty forms of organic matter.
40Air and lung: Aspergillosis Lung infarct (left), aspergilloma (right). Diseases initiated by spores entering the lungs.Aspergillus with infectious spores(3-6 microns).
413.) 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.
42Candidiasis (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.
43Conclusions1.) 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.
492. Cutaneus Mycoses Infeksi jamur pada jaringan berkeratin (kulit, rambut dankuku)Jamur mensekresi keratinase, suatu enzym yang mendegradasi keratin.Infeksi ditransmisikan melalui kontak langsung dengan kulit, kuku atau rambut yang terinfeksi.
50Cutaneus mycoses Disease Causative organisms Incidence Dermatophytosis Ringworm of the scalp, glabrous skin and nails.Dermatophytes (Microsporum, Trichophyton, Epidermophyton)CommonCandidiasis of skin and and nails.Candida albicans and related species.
51Dermatophytosis: Ringworm of the scalp, glabrous skin and nails Disease SymptomsTinea capitis ringworm lesion of scalpTinea corporis ringworm lesion of trunk, arms, legs Tinea manusringworm lesion of handTinea cruris "jock itch"ringworm lesion of groinTinea pedis"athlete's foot"ringworm lesion of footTinea unguiuminfection of nailsEctothrixinfection of hair shaft surface Endothrixinfection of hair shaft interior
52Dermatophytosis: Clinical Manifestation Tinea Pedis: is transmitted via the feet by desquamated skin scales in substrates like carpet and matting
54Dermatophytosis: 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
55Dermatophytosis: Laboratoy Diagnosis Spesimen: Skin Scrapings, nail scrapings and epilated hairsMethod:Direct Microscopy: KOH 10-20% and ink parkerCulture: Sabouraud's dextrose agar containing cycloheximide incubated at 26-28C for 4 weeks
573. 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.
583. Subcutaneus Mycoses Disease Causative organisms Incidence Clinical manifestationSporotrichosisSporothrix schenckii RareNodules and ulcers along lymphatics at site of inoculationChromoblastomycosis Fonsecaea, Phialophora, Cladosporium etc.Warty nodules that progress to "cauliflower-like" appearance at site of inoculation Mycotic mycetomaPseudallescheria, Madurella, Acremonium, Exophiala etc.Draining sinus tracts at site of inoculation
59Subcutaneus mycoses: SPOROTRICHOSIS Sinonim: Rose Garnener’s diseaseManifestasi klinisCutaneus sporotrichosisInfeksi sistemik
60Pewarnaan GMS pada spesimen biopsi SporotrichosisCharacteristic lymphadenopathy.Pewarnaan GMS pada spesimen biopsi
61Subcutaneus mycoses: Chromoblastomycosis Penyebab: Fonsecaea pedrosoi, Fonsecaea compacta, Phialophora verrucosa, Cladosporium carrioniiManifestasi klinik:Nodule verrucous atau plaqueSering terjadi di daerah tropis yang lembabKebanyakan pada kaki, didahului dgn luka ( bisa pada bagian tubuh lain)Walaupun jarang, dapat menyerang otak (menyebar secra hematogen)
62Chromomycosis Etiologic agent showing dematiaceous hyphae and spores 10-year old case
63Subcutaneus mycoses: MYCETOMA Sinonim: Madura footPenyebab: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 kumanDitemukannya granule/grains sangat penting untuk diagnosabbrp jamur/bakteri penyebab mycetoma dapat di isolasi dari tanah/ pohon.
64Mycetomas 15-year old case of mycetoma One of many etiologic agents .Note hyphae and spores which live in nature. Fusarium sp.
65*more common in endemic areas. 4. Systemic MycosesMenginfeksi jaringan/organ secara sistemikBiasanya disebabkan jamur yang hidup di tanah.Disease Causative organisms IncidenceHistoplasmosisHistoplasma capsulatum Histoplasma dubosiiRare*Coccidioidomycosis Coccidioides immitis BlastomycosisBlastomyces dermatitidis ParacoccidioidomycosisParacoccidioides brasiliensis SporotrichosisSporothrix schenkiiRarePenicilliosis marnefffeiPenicillium marneffei*more common in endemic areas.
66Histoplasmosisintracellular infection of the reticuloendothelial systemcaused by the inhalation of conidia from Histoplasma capsulatumIsolation: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
67HISTOPLASSMOSIS 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.
69COCCIDIOIDOMYCOSISinitially: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.
70Coccidioidomycosis (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.
71fever, 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 .
725. Opportunistic Mycoses Adalah infeksi yang terjadi pada manusia/hewan dengan sistem pertahanan tubuh yang menurun :pasien AIDS, pasien kankerIndividu yg mendapat terapi antibiotik spektrum luasneonatus / individu yang sangat tuaDiabetes melitusResipien organ transplanTerapi steroidPada sistem imun yang baik tidak menyebabkan penyakit.Penyebab: Flora normal ataupun fungi yang ada di lingkungan
735. Opportunistic Infection DiseaseCausative organismsIncidenceCandidiasis Candida albicans and related species.CommonCryptococcosisCryptococcus neoformans Rare/CommonAspergillosisAspergillus fumigatus etc. RareZygomycosis (Mucormycosis)Rhizopus, Mucor, Rhizomucor, Absidia etc.PneumocystosisPneumocystis carinii
74Opportunistic mycoses: Candidiasis Candidiasis also called as Monoliasis,Can infect Skin, Mucosa, or Internal OrgansNormal floraExist in Mouth, Gastrointestinal tract, Vagina, skin in 20 % of normal Individuals.Colonization increases with age,in pregnancy, HospitalizationImportant etiological agent presenting as opportunistic infection in Diabetus and HIV patients
75Clinical 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.
76Laboratory diagnosis Clinical specimen: Skin scrapings, Mucosal scrapping,Vaginal secretionsBlood ans other body fluidMethod:Direct mikroskopicCultures : on Sabouraud's Glucose agarPCR
78Morphology A true yeast Round 4 – 10 microns Surrounded by Mucopolysaccharide capsule.Negative staining with India Ink and Nigrosin60% of the infected prove positive by India Ink preparation on examination of CSF
79Life cycle of C.neofromans Found in wild/Domesticated birds (Pigeon) and eucalyptustree.Pigeons carry C.neofromans, but do not get infected.
80PathogenesisEnters through lungs - inhalation of Basidiospores of C neoformansEnters deep into lungs.Self limiting in most cases,Pulmonary infections can occur.Present as discrete nodules - Cryptococcoma.
81Pathogenesis Can infect normal humans Abnormalities of T lymphocyte function aggravates the clinical manifestations (In AIDS % develop Cryptococcosis)Clinical manifestation: Chronic meningitis , Meningo encephalitis ,head ache low grade fever,Visual abnormalities ,Coma – fatalCan manifest with involvement of ,Skin,mucosa,organs,Bones,and as Disseminated form.Can mimic like Tuberculosis
82Laboratory Diagnosis. Mikroskopic: Indian ink staining, Gram staining Kultur :Cultures on Sabouraud dextrose agarSerologis: detection of Capsular antigen
83Avoid contact with Birds TreatmentImmune competent - Antifungal drugAIDS patients are not totally cured , Relapses are frequent with fatal outcome.Prevention:Avoid contact with Birds
87Morphology 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
88Pathogenesis - varied clinical presentations Allergic Aspergillosis – Atopic individuals, with elevated IgE levels10-20% of Asthmatics react to A.fumigatusAllergic alveoitis follows particularly heavy and repeated exposure to larger number of sporesMaltsters Lung – causes allergic alveolitis, who handle barley on which A.claveus has sporulated during malting process
89PathogenesisAspergilloma – 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 productionHaemoptysis occurs due to invasion of blood vessels
90Pathogenesis Invasive Aspergillosis occurs in immunocompromised with underlying diseaseA.fumigatus >>Fungus invades blood vessels, causes thrombosis septic emboliCan spread to Kidney and heart.