Viral Zoonosis Rabies
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Viral Zoonosis (Rabies)
Titiek Djannatun
Bagian Mikrobiologi- Fakultas Kedokteran
Universitas YARSI
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Definition
Zooneses are diseases of vertebrate animals that can be transmitted to man: either directly or indirectly through an
insect vector.
When an insect vector is involved, the disease is also known as an arboviral disease.
However, not all arboviral diseases are zoonosis: where the transmission cycle takes place exclusively between insect
vector and human e.g. dengue and urban yellow fever.
Examples of viral zoonoses that can be transmitted to man directly include rabies, hantaviruses, lassa and ebola fevers.
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KLASIFIKASI, TAKSONOMI &
NOMENKLATUR
FAMILIA : Rhabdoviridae
GENUS : Lyssavirus
Ephemerovirus
Vesiculovirus
SPESIES : Rabies virus, lagos bat, Mokola virus, Devenhage virus, European bat virus 1 & 2, Australian bat virus (Lyssavirus)
VIRUS RNA ,SS,POLARITAS NEGATIF, NON SEGMENTED
INFEKSI AKUT SSP DAN MEMATIKAN
VIRUS DITULARKAN MELALUI GIGITAN BINATANG BUAS (GILA)
TERSEBAR LUAS DIANTARA RESERVOAR BINATANG
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SIFAT PENTING RHABDOVIRUS
VIRION BERBENTUK SPT PELURU, DIAMETER 75X180NM
KOMPOSISI RNA (4%), PROTEIN (67%), LIPID (26%), KH (3%)
GENOM SS RNA, LURUS, NON SEGMENTED, - SENSE, BM 4,6
JUTA, 12 kb
PROTEIN 1 GLIKOPROTEIN ENVELOPE
REPLIKASI SITOPLASMA, VIRION BERTUNAS DI M PLASMA
ENVELOPE ADA
CIRI KHAS BARISAN VIRUS YG LEBAR DG KISARAN INANG
LUAS MRPK GRUP VIRUS YG MEMATIKAN
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Rabies Virus
member of the Lyassavirus of the Rhabdoviridae.
ssRNA enveloped virus, characteristic bullet-shaped appearance with 6-7 nm spike projections.
virion 130-240nm * 80nm
-ve stranded RNA codes for 5 proteins; G, M, N, L, S
Exceedingly wide range of hosts.
There are 5 other members of Lyassavirus : Mokola, Lagosbat, Duvenhage, EBL-1, and EBL-2.
Duvenhage and EBL-2 have been associated with human rabies.
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STRUKTUR VIRUS
UKURAN Pj 180 nm, Lebar 75 nm
Genom mengkode 5 protein
Nukleoprotein (N)
Phosphoprotein (P)
matrix protein (M)
Glikoprotein (G)
Polymerase (L)
Komponen struktural core Ribonukleoprotein (RNP) dikelilingi envelope.
Genom RNA nukleoprotein/kapsid (heliks)
N, L, P genom RNA
M envelope membran
G tonjolan glikoprotein envelope
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Rabies Virus
Structure of rabies virus (Source: CDC)
Rabies virus particles
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Viral Structure
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SIFAT FISIKA- KIMIA
PADA 40C TAHAN SELAMA SEMINGGU
DIINAKTIVASI OLEH CO2
PENYIMPANAN DALAM VIAL BERTUTUP GELAS PADA DRY ICE
MATI SINAR UV ATAU SINAR MATAHARI
PEMANASAN (1 JAM PADA 500C)
LEMAK (ETHER, 0,1% NATRIUM DEOKSIKHOLAT)
TRIPSIN
DETERJEN
pH EXTRIM
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REPLIKASI
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Epidemiology
Rabies is a zoonosis which is prevalent in wildlife. The main
animals involved differs from continent to continent.
Europe fox, bats
Middle East wolf, dog
Asia dog
Africa dog, mongoose, antelope
N America foxes, skunks, raccoons,
insectivorous bats
S America dog, vampire bats
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KERENTANAN HEWAN THD RABIES VIRUS
SANGAT
TINGGI
TINGGI SEDANG RENDAH
RUBAH HAMSTER ANJING TUPAI
COYOTE MUSANG LEMBU
SERIGALA RAKUN DOMBA
ANJING
HUTAN
KUCING KAMBING
KELELAWAR KUDA
KELINCI PRIMATA BUKAN
MANUSIA
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WABAH RABIES
INDONESIA 2004-2008 15.000 DIGIGIT
BADUNG, BALI VAKSIN 20.000 ANJING
TH 2008 14.106 ORANG: 9565 DIBERI VAKSIN DAN OBAT; 85 RABIES
BALI 1700 ORANG
PENYEBAB: POPULASI ANJING TDK TERKENDALI KRN LEMAHNYA SISTEM DETEKSI DINI DAN
EVALUASI PERIODIK SURVEY SEROLOGI ANTIBODI DARI HEWAN SUMBER PENULARAN
HARUSNYA DILAKUKAN PERIODIK
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Pathogenesis
The commonest mode of transmission in man is by the bite of a rabid animal, usually a dog. Rabies is an acute
infection of the CNS which is almost invariably fatal.
Following inoculation, the virus replicates in the striated or connective tissue at the site of inoculation and enters the
peripheral nerves through the neuromuscular junction.
It then spreads to the CNS in the endoneurium of the Schwann cells.
Terminally, there is widespread CNS involvement but few neurons infected with the virus show structural
abnormalities. The nature of the profound disorder is still
not understood.
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Viral cycle
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Viral cycle
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Viral Pathogenesis
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PATOGENESA & PATOLOGI
VIRUS OTOT/JAR IKAT (BKBG BIAK) , KADANG TANPA REPLIKASI LOKAL SARAF TEPI (NEUROMUSCULAR JUNCTION) SSP BERBIAK DI OTAK SARAF TEPI KEL LUDAH & JAR LAIN.
VIRUS DAPAT DITEMUKAN
KEL LUDAH SUBMAXILLA (TITER TERTINGGI)
PANKREAS, GINJAL, HATI , RETINA, KORNEA
VIRUS BLM PERNAH DIISOLASI DARI DARAH PASIEN TERINFEKSI
VIRUS MEMBENTUK BADAN INKLUSI INTRASITOPLASMA, ASIDOFILIK PD SEL SARAF TERINFEKSI BADAN NEGRI
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PATOGENESA & PATOLOGI
KERENTANAN & MASA INKUBASI TERGANTUNG :
UMUR PASIEN
LATAR BELAKANG GENETIK
STATUS IMMUN
STRAIN VIRUS PATOGENITAS VIRUS JUMLAH INOKULUM JUMLAH VIRUS YANG MASUK BERATNYA LASERASI DALAM DAN PARAHNYA LUKA
BEKAS GIGITAN, JUMLAH LUKA GIGITAN, JUMLAH SYARAF DI SEKITAR GIGITAN
JARAK DARI PORT DTRY SSP (LOKASI LUKA)
GIGITAN DI KEPALA/WAJAH MASA INKUBASI PENDEK, SERANGAN TINGGI
GIGITAN PADA KAKI KEMATIAN RENDAH
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GEJALA KLINIS
ENSEFALITIS AKUT, FULMINANT, FATAL
MASA INKUBASI 1 MINGGU, 1-2 BULAN, BBRP TH (> 6 TH) :
HEWAN TIMBUL GJL > 2 MINGGU (20 HARI-8 MINGGU)
MANUSIA TIMBUL GJL 2-3 MINGGU SMP 1 TAHUN
FASE KLINIS
FASE PRODOMAL PENDEK
FASE NEUROLOGI AKUT
KOMA
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GEJALA KLINIS
FASE PRODOMAL PENDEK :
2-10 HARI
MALAISE, ANOREXIA, NYERI KEPALA, FOTOPOBIA, MUAL, MUNTAH NYERI TENGGOROKAN, DEMAM
FASE NEUROLOGI AKUT :
GELISAH, CEMAS, HALUSINASI, LAKRIMASI, DILATASI PUPIL, SALIVASI (AKTIVITAS MENELAN SBBK SPASME & NYERI OTOT TENGGOROKAN), BERKERINGAT, SEBAG HIDROPOBIA KEJANG/KOMA KEMATIAN (2-7 HARI STLH ONSET) KRN KELUMPUHAN PERNAFASAN
RABIES PARALITIK TERJADI SEKITAR 20% PASIEN AKIBAT TERINFEKSI VIRUS RABIES KELELAWAR
BBRP BTHN 30 HARI, TP JARANG YANG DPT SEMBUH & BTAHAN HIDUP
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GEJALA PADA HEWAN
BENTUK GANAS (FURIOS RABIES): MASA EKSITASI PANJANG, UMUMNYA AKAN MATI 2-5 HR
STLH TANDA-TANDA TERLIHAT HEWAN MENJADI GALAK DAN PENAKUT, MEMBANGKANG PERINTAH MAJIKAN, NAFSU MAKAN HILANG, HIPERSALIVASI, EKOR DIANTARA 2 PAHA
BENTUK DIAM (DUMB RABIES): MASA EKSITASI PENDEK, PARALISA CEPAT TERJADI
BERSEMBUNYI DI TEMPAT GELAP DAN SEJUK, KEJANG2 DALAM WKT SINGKAT, LUMPUH TDK DAPAT MENELAN, HIPERSALIVASI
BENTUK ASYMPTOMATIS: TANPA GEJALA, TIBA-TIBA MATI
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Dumb Rabies
Dumb Rabies, manifested as depresion and an
attempt at self-imposed isolation
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GEJALA PADA MANUSIA
NAFSU MAKAN HILANG, SAKIT KEPALA, TIDAK BISA TIDUR, DEMAM TINGGI, MUAL DAN
MUNTAH2
RASA PANAS PADA TEMPAT GIGITAN
TAKUT AIR, SUARA KERAS, CAHAYA DAN ANGIN
AIR LIUR, AIR MATA KELUAR BERLEBIHAN
KEJANG2 DISUSUL KELUMPUHAN
BIASANYA MENINGGAL DALAM WAKTU 4-6 HR SETELAH GEJALA KLINIS PERTAMA TIMBUL
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GEJALA PADA MANUSIA
KALAU DIGIGIT DEKAT LEHER/KEPALA AKUT:
DEMAM TINGGI
KEJANG2 OTOT
MULUT BERBUSA
FOTOPHOBIA
KESADARAN MENURUN
BERTERIAK-TERIAK
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Human rabies
Hospitalized human rabies, who was
restrained while bedridden
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Human rabies
Hospitalized human rabies victim in
restrains
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Laboratory Diagnosis
Histopathology - Negri bodies are pathognomonic of rabies. However, Negri bodies are only present in 71% of cases.
Rapid virus antigen detection - in recent years, virus antigen detection by IF had become widely used. Corneal impressions or neck skin biopsy are taken. The Direct Fluorescent Antibody test (DFA) is commonly used.
Virus cultivation - The most definitive means of diagnosis is by virus cultivation from saliva and infected tissue. Cell cultures may be used or more commonly, the specimen is inoculated intracerebrally into infant mice. Because of the difficulties involved, this is rarely offered by diagnostic laboratories.
Serology - circulating antibodies appear slowly in the course of infection but they are usually present by the time of onset of clinical symptoms.
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DIAGNOSA LABORATORIUM
ANTIGEN RABIES/ASAM NUKLEAT
IMMUNOFLUORESCENS, PCR (JAR OTAK/KORNEA
ISOLASI VIRUS
INTRACEREBRAL PADA TIKUS YG BLM DISAPIH ENSEFALITIS & KEMATIAN
SEROLOGI
IMMUNOFLUORESCENS, TES Nt
OBSERVASI HEWAN
SELAMA 10 HARI PADA HEWAN RESERVOAR
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Negri Body in neuron cell
(source: CDC)
Positive DFA test (Source: CDC
Diagnosis of Rabies
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Characteristic Negri Bodies
Histopathologic features of rabies, brain. Characteristic
Negri Bodies are present within a Purkinye cell of the
cerebellum; patient died of rabies
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Management and Prevention
Pre-exposure prophylaxis - Inactivated rabies vaccine may be administered to persons at increased risk of being exposed to rabies e.g. vets, animal handlers, laboratory workers etc.
Post-exposure prophylaxis - In cases of animal bites, dogs and cats in a rabies endemic area should be held for 10 days for observation. If signs develop, they should be killed and their tissue.
Wild animals are not observed but if captured, the animal should be killed and examined. The essential components of postexposure prophylaxis are the local treatment of wounds and active and passive immunization.
Once rabies is established, there is nothing much that could be done except intensive supportive care. To date, only 2 persons with proven
rabies have survived.
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Postexposure Prophylaxis
Wound treatment - surgical debridement should be carried out. Experimentally, the incidence of rabies in animals can be reduced by local treatment alone.
Passive immunization - human rabies immunoglobulin around the area of the wound; to be supplemented with an i.m. dose to confer short term protection.
Active immunization - the human diploid cell vaccine is the best preparation available. The vaccine is usually administered into the deltoid region, and 5 doses are usually given.
There is convincing evidence that combined treatment with rabies immunoglobulin and active immunization is much more effective than active immunization alone. Equine rabies immunoglobulin (ERIG) is available in many countries and is considerably cheaper than HRIG.
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PENANGGULANGAN
KASUS NON AKUT:
CUCI LUKA DG SABUN/DETERGEN SLM 5-10 MENIT DI BAWAH AIR
BERI ALKOHOL 70%/YODIUM
BERI Ig ANTI RABIES DAN VAKSIN
HEWAN KIRIM KE DINAS PETERNAKAN
ORANG YANG DIGIGIT RS KHUSUS INFEKSI
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PENANGGULANGAN
KASUS AKUT:
VAKSIN EFEK SAMPING: MENINGITIS + GJL SEPERTI RABIES
YODIUM TDK MEMBANTU KRN VIRUS SDH MSK
Ig ANTI RABIES CEGAH VIRUS TDK MENYEBAR KE SYARAF OTAK
ISOLASI PENDERITA BISA MENULARKAN
OBAT TDK ADA, TERAPI SYMPTOM: ANTI KEJANG, OBAT CEGAH INFEKSI SEKUNDER,
OBAT PENENANG
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Rabies Vaccines
The vaccines which are available for humans are present are inactivated whole
virus vaccines.
Nervous Tissue Preparation e.g. Semple Vaccine - associated with the rare complication of demyelinating allergic encephalitis.
Duck Embryo Vaccine - this vaccine strain is grown in embryonated duck eggs This vaccine has a lower risk of allergic encephalitis but is considerably
less immunogenic.
Human Diploid Cell Vaccine (HDCV) - this is currently the best vaccine available with an efficacy rate of nearly 100% and rarely any severe reactions.
However it is very expensive.
Other Cell culture Vaccines - because of the expense of HDCV, other cell culture vaccines are being developed for developing countries. However
recent data suggests that a much reduced dose of HDCV given intradermally
may be just be effective.
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IMMUNITAS & PENCEGAHAN
VAKSINASI :
VAKSIN SEL DIPLOID MANUSIA (HDCV)
VAKSIN RABIES TERABSORPSI (RVA)
VAKSI SEL EMBRIO AYAM DIMURNIKAN (PCEC)
VAKSIN JARINGAN SARAF
VAKSIN EMBRIO BEBEK
VIRUS HIDUP DILEMAHKAN
TIPE ANTIBODI RABIES :
Ig RABIES MANUSIA (HRIG)
SERUM ANTIRABIES KUDA
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IMMUNITAS & PENCEGAHAN
PENCEGAHAN SEBELUM PEMAPARAN :
VAKSINASI PADA INDIVIDU BERESIKO TINGGI
PENCEGAHAN SETELAH PEMAPARAN :
PENATALAKSANAAN & PENGENDALIAN :
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Control of Rabies
Urban - canine rabies accounts for more than 99% of all human rabies. Control measures against canine rabies include;
stray dog control.
Vaccination of dogs
quarantine of imported animals
Wildlife - this is much more difficult to control than canine rabies. However, there are on-going trials in Europe where bait
containing rabies vaccine is given to foxes. Success had been
reported in Switzerland.
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KLB Rabies
Jumlah yang digigit meningkat
Jumlah vaksin terbatas
Vaksin rabies pasca paparan mahal (VeroRab 4x suntikan/bulan
Sumber: muntah, ludah pasien
Sulit edukasi masyarakat untuk:
Eradikasi anjing liar
Henti makan daging anjing
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Skor LARAT
LARAT: nama titik terluar NKRI, yang berbatasan langsung dengan Samudra Hindia
Probability/Peluang kejadian Rabies pada pasien gigitan anjing saat KLB
Rumus 1
1 + e-(F)
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Skor LARAT
F = 6,3 + 1,6 (selisih waktu gigit anjing < 2 bulan) + 1,3 (lokasi luka gigitan di kepala,
wajah, leher, dada, atau punggung) + 2,5
(karakteristik anjing dominan ciri rabies) + 2
(anjing mati sendiri/dibunuh namun diketahui
telah digigit anjing yang mati sendiri berasal
dari korban).
e = Hasil analisis multivarian model epidemiologi
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Sistem skoring prediksi rabies pada pasien gigitan anjing saat KLB Rabies
No Variasi Kategori Skor
1 Selisih waktu gigitan anjing < 2 bulan 2 bulan
2 0
2 Lokasi luka gigitan anjing Kepala, wajah, leher, dada, punggung Lengan, tangan, perut, tungkai, kaki
1 0
3 Karakteristik anjing (ada 7 karakteristik)
Dominan Rabies ( 4 sifat) Tidak dominan Rabies (< 4 sifat)
3 0
4 Akibat kematian anjing Anjing mati sendiri, atau anjing dibunuh namun diperoleh informasi bahwa anjing tersebut mati telah digigit anjing lain yang mati sendiri Anjing dibunuh, tidak mati, tidak tahu
3 0
Skor maksimum Skor minimum
9 0
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Analisis sensitivitas dan
spesifisitas pada ROC curve, skor
5 memberikan prediksi Rabies
sehingga perlu mendapat prioritas
vaksinasi di saat KLB