Suatu Cryptococcus neoformans yeast, oval, dengan kapsul karbohidrat yang tebal dlm kultur & cairan di jaringan, tidak bersifat dimorfik Termasuk infe

Cryptococcus yp neoformans Dr. Tetty Aman Nasution, M Med Sc Departemen Mikrobiologi FKFK-USU MEDAN

Cryptococcus neoformans „

Suatu

yeast, y

oval oval,,

dengan g

kapsul p

karbohidrat yang tebal dlm kultur & cairan di jaringan, j i tidak tid k bersifat b if t dimorfik di fik „

Termasuk infeksi jjamur opportunistik pp

„

The most common life life--threatening fungal disease in AIDS patients

Cryptococcus neoformans „ „ „ „ „

Invasive fungal infection Increasingly prevalent with increasing numbers of immunocompromised patients. An encapsulated yeast C. neoformans Æ major pathogenic member of the genus S b classified Sub l ifi d iinto t 4 serotypes t and d 2 varieties i ti „ Serotypes based upon capsular agglutination reactions, types A, B, C, D „ Serotype A now classified as variety grubii „ Serotypes B + C variety gattii „ Serotype Serot pe D variety ariet neoformans

Cryptococcus neoformans lif lifecycle l „

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Exists in asexual and sexual forms, with the asexual form existing as a yeast, which reproduces by budding, the only form associated with human infection. Produces white mucoid colonies in vitro which become visible within 48 hours Thick capsule visible in India ink suspension . Capsule has important antiphagocytic properties

Infeksi Jamur Opportunistik Penyebab Jamur saprophyte di alam atau juga sebagai normal flora dlm tubuh manusia Host yang dikenai Immunosupresi, immunodefisensi, keganasan

Infeksi Jamur Opportunistik „ „ „ „

Candidiasis Cryptococcosis Aspergillosis Zygomycosis

***ANY fungus found in nature may give rise to ***ANY opportunistic mycoses ***

CRYPTOCOCCOSIS „

Kadang2 dpt terjadi pada orang normal

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Infeksi terjadi j secara exogenous g

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Pathogenesis :

inhalasi yeasts melalui

saluran pernapasan „

Dapat bersifat asimptomatik

CRYPTOCOCCOSIS „

Gejala pada paru paru--paru Æ non spesifik, spesifik bisa tjd pneumonia.

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Jika tjd pd orang normal Æ penghirupan yeast dlm jumlah yg banyak Æ penyakit sistemik progresif.

Cryptococcus neoformans Morfologi & Identifikasi Natural reservoir: reservoir: „ Soil/tanah, bird droppings/tinja burung (terutama merpati) yang sudah mengering Microscopic:: Microscopic „ Bentuk: bulat atau oval, diameter 4-12 12μ μm,, sering g bertunas „ Encapsulated yeast ( terlihat dgn menggunakan India ink)

Cryptococcus neoformans ecology l „

Var g grubii and var neoformans Found worldwide in soil contaminated by bird droppings (chickens and pigeons) pigeons), roosting sites and rotting vegetation „ Pigeons do not become infected, inhibited by body t temperature t off > 40 o C „ Cryptococcus can be found in pigeon GI tract „ Outbreaks of disease not associated with pigeon roosting areas „

Cryptococcus neoformans ecology l „

Var gattii „ Never cultured from bird guano „ Flowering river red gums (Eucalyptus (Eucalyptus camaldulensis)) and forest red gums (E. camaldulensis (E. tereticornis)) „ These trees have been widely exported around the world

Cryptococcus neoformans Morfologi & Identifikasi Macroscopic:: Macroscopic „

Pada Saboroud Dextrose Agar (SDA), suhu kamar Æ koloni kecoklatan kecoklatan, mucoid, mucoid dan mengkilat

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Kultur tidak meragi karbohidrat

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Mengasimilasi glukosa, maltosa, sukrosa, galaktosa, tetapi laktosa Æ tidak

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Urea dihidrolisis

Cryptococcus neoformans Serotypes:: Serotypes „

4 tipe serologik polisakarida kapsul (A,B,C,D) Æ kebanyakan adalah serotype A

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Antigen kapsul dapat larut dlm cairan spinal, serum atau air kemih serum,

Cryptococcus neoformans „

D t k id Deteksi dengan antiserum ti spesifik ifik tterhadap h d karbohidrat yaitu Latex Particle Agglutination Test

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Cara kerja: j partikel p latex yang y g telah dilapisi p Antibodi spesifik akan teragglutinasi dengan antigen homolog dari yeast yang diperiksa

Cryptococcus neoformans „

Pathogenicity factors: factors:

a. Antigen pada kapsul b. Menghasilkan pigmen coklat pd bird seed agar/ caffeic acid medium Æ tanda diagnostik c. Tumbuh baik pd suhu 37° 37°C dlm perbenihan bi biasa yg tdk mengandung d sikloheksimid ikl h k i id

Clinical Manifestations „

Pulmonary cryptococcosis „ „ „

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Asymptomatic carriage may occur in healthy people as well as those with chronic lung disease May experience a self limited pneumonia Invasive chronic pulmonary disease may occur and may disseminate to the CNS

CNS disease „ „ „

M i iti (85%) Meningitis (85%), meningoencephalitis, i h liti cryptococcoma t Generally symptoms more insidious and of longer duration in the non--immunosuppressed non Hi h burden Higher b d off organisms i in i AIDS, AIDS with ith variable i bl iinflammatory fl t response, which parallels degree of immunosuppression

Clinical manifestations „

Cutaneous cryptococcosis yp „ „

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Bone and joint disease „

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Lytic lesions in up to 10% with disseminated disease

Ocular cryptococcosis „

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Ulcerated or nodular lesions – usually poor prognosis in disseminated disease Cellulitis

Rare, other than pressure effects

Genitourinary disease „

Prostate acts as sanctuary site in immunosuppressed

CRYPTOCOCCOSIS Gambaran Klinik 1 1.

PULMONARY : Asimptomatik, gejala paru non spesifik, sub kli ik klinik.

2.

DISSEMINATED :

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Meningitis acute/chronic Æ gejala mirip tumor otak otak, abses otak otak, peny peny. degeneratif SSP, meningitis mycobacteria atau jamur

CRYPTOCOCCOSIS Gambaran Klinik 2.

DISSEMINATED :

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Lesi pada paru paru--paru, paru kulit kulit, dan organ organ-organ lain

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Manifestasi klinis yg paling sering : meningitis kronik, berkembang lambat, remisi spontan, terjadi beberapa kali eksaserbasi. k b i

Diagnosis C Cryptococcus neoformans f „ „

High index of suspicion needed Lumbar pucture „ Measure + record opening pressure „ Repeat at least fortnightly during therapy and daily if pressure > 25 cmH2O „ India ink examination „ CSF WCC (usually mononuclears) typically low (< 50) in th those with ith advanced d d iimmunosuppression i „ CSF glucose + protein often only minimally abnormal „ Cryptococcal antigen assay „ Rapid diagnostic test „ Rare false positives „ Titre generally correlates to organism burden „ Serum assay useful screen in AIDS patients

Diagnosis C Cryptococcus neoformans f „

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Extraneural cultures „ Occasionally positive from another site „ Full evaluation needed to exclude disseminated disease, or CNS disease Radiology „ Detection of cryptococcomas „ May detect hydrocephalus -> need for shunt

CRYPTOCOCCOSIS Diagnosis „

Bahan spesimen: ) Cairan spinal (CSF) (CSF), ) Sputum, ) Aspirasi dari lesi kulit, ) Exudat, udat, ) Air kemih, ) Serum

CRYPTOCOCCOSIS Diagnosis „

Pemeriksaan:: Pemeriksaan * dalam keadaan basah : direct examination, examination, atau dengan India ink (kapsul terlihat besar besar, menonjol di sekitar sel bertunas, tdk berwarna) *d dalam l kkeadaan d k i : kering pewarnaan immunoflouresensi

CRYPTOCOCCOSIS Diagnosis „

Kultur Saboroud Agar (SDA), perbenihan b ih llain i Æ sikloheksimid ikl h k i id ((--)

CRYPTOCOCCOSIS Diagnosis „

Serology deteksi kapsul antigen didalam cairan spinal dan serum dengan Latex Particle Agglutination T t Ætiter Test tit Antigen A ti akan k meninggi i i *Cara serologis ini, 90% positif pada pasien meningitis kriptokokosis

CRYPTOCOCCOSIS Pengobatan „

Kombinasi Amphotericin p B + flucytosine y Æ pengobatan pilihan untuk meningitis k i t k kk i kriptokokkosis

CRYPTOCOCCOSIS Pengobatan „

Walaupun Amphotericin B dpt menyembuhkan sebagian besar pasien meningitis kriptokokkosis, ttp penghentian Amphotericin B pada pasien AIDS dgn kriptokokkosis akan menyebabkan kekambuhan.

CRYPTOCOCCOSIS Pengobatan „

Flukonazol dapat memasuki cairan CSF dengan baik Æ meningitis kriptokokkosis

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Ketokonazol tdk berguna utk pasien dengan meningitis kriptokokkosis

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Pada pasien AIDS Æ terapi supresif jangka panjang dengan flukonazol oral

Cryptococcus - epidemiology „

Increasing gp proportions p of p patients have an underlying immune deficiency – virtually all var neoformans or var grubii „

HIV/AIDS „ „ „

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Accounts for up to 50% cryptococcal infections CD 4 < 200 Incidence has declined in Australia since advent HAART

Prolonged steroid therapy Organ transplantation Malignancy Sarcoidosis

Cryptococcus neoformans var gattii „

In contrast to var neoformans, neoformans, var gattii geographically restricted: „ „ „ „

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Australia, PNG N. Africa and Mediterranean India, SE Asia Mexico,, Brazil,, Paraguay, g y, S California

Commonly non non--immunocompromised hosts Large mass lesions (cryptococcomas) common, resulting in significant morbidity.

Epidemiologi & Pencegahan „

Sumber utama infeksi: kotoran burung (terutama merpati) yang mengandung Cryptococcus

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Organisme tumbuh subur dalam ekskreta burung merpati (nitrogenous waste creatinine) ttp burung creatinine), b r ng tsb tidak terinfeksi terinfeksi.

Epidemiologi & Pencegahan „

Cara pengendalian: pengurangan populasi burung merpati & dekontaminasi tempat burung bersarang dengan alkali

Budding yeast Cryptococcus neoformans

Cryptococcus neoformans

Tortora et.al; Figure 22.14