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
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
Infeksi terjadi j secara exogenous g
Pathogenesis :
inhalasi yeasts melalui
saluran pernapasan
Dapat bersifat asimptomatik
CRYPTOCOCCOSIS
Gejala pada paru paru--paru Æ non spesifik, spesifik bisa tjd pneumonia.
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
Kultur tidak meragi karbohidrat
Mengasimilasi glukosa, maltosa, sukrosa, galaktosa, tetapi laktosa Æ tidak
Urea dihidrolisis
Cryptococcus neoformans Serotypes:: Serotypes
4 tipe serologik polisakarida kapsul (A,B,C,D) Æ kebanyakan adalah serotype A
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
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
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
Bone and joint disease
Lytic lesions in up to 10% with disseminated disease
Ocular cryptococcosis
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 :
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 :
Lesi pada paru paru--paru, paru kulit kulit, dan organ organ-organ lain
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
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
Ketokonazol tdk berguna utk pasien dengan meningitis kriptokokkosis
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
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:
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
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