ViralZoonosis(Rabies)Titiek DjannatunBagian Mikrobiologi-
Fakultas KedokteranUniversitas YARSIDefinitionZooneses are diseases
of vertebrate animals that can betransmitted to man: either
directly or indirectly through an insect vector.When an insect
vector is involved, the disease is alsoknown 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 mandirectly include rabies,
hantaviruses, lassa and ebola fevers.KLASIFIKASI,
TAKSONOMINOMENKLATURFAMILIA : RhabdoviridaeGENUS : Lyssavirus
Ephemerovirus Vesiculovirus&SPESIES : Rabies virus, lagos bat,
Mokola virus, Devenhagevirus, European bat virus 1 & 2,
Australian bat virus(Lyssavirus)VIRUS RNA ,SS,POLARITAS NEGATIF,
NON SEGMENTEDINFEKSI AKUT SSP DAN MEMATIKANVIRUS DITULARKAN MELALUI
GIGITAN BINATANG BUAS (GILA)TERSEBAR LUAS DIANTARA RESERVOAR
BINATANGSIFAT PENTING RHABDOVIRUSVIRIONBERBENTUK SPT PELURU,
DIAMETER 75X180NMKOMPOSISIRNA (4%), PROTEIN (67%), LIPID (26%), KH
(3%)GENOMSS RNA, LURUS, NON SEGMENTED, - SENSE, BM 4,6JUTA, 12
kbPROTEIN1 GLIKOPROTEIN ENVELOPEREPLIKASISITOPLASMA, VIRION
BERTUNAS DI M PLASMAENVELOPEADACIRI KHASBARISAN VIRUS YG LEBAR DG
KISARAN INANG LUAS MRPK GRUP VIRUS YG MEMATIKANRabies Virusmember
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.STRUKTURVIRUSUKURAN Pj 180 nm, Lebar 75 nmGenom mengkode 5
protein Nukleoprotein (N) Phosphoprotein (P) matrix protein (M)
Glikoprotein (G) Polymerase (L)Komponen struktural core
Ribonukleoprotein (RNP) dikelilingienvelope.Genom RNA
nukleoprotein/kapsid (heliks) N, L, P genom RNAM envelope membranG
tonjolan glikoprotein envelopeRabiesVirusStructure of rabies virus
(Source: CDC)Rabies virus particlesViral StructureSIFAT FISIKA-
KIMIAPADA 40C TAHAN SELAMA SEMINGGUDIINAKTIVASI OLEH CO2PENYIMPANAN
DALAM VIAL BERTUTUP GELAS PADA DRY ICEMATI SINAR UV ATAU SINAR
MATAHARI PEMANASAN (1 JAM PADA 500C) LEMAK (ETHER, 0,1% NATRIUM
DEOKSIKHOLAT) TRIPSIN DETERJEN pH EXTRIMREPLIKASIEpidemiologyRabies
is a zoonosis which is prevalent in wildlife.Themainanimals
involvedEuropediffers from continent to continent.fox, bats wolf,
dog dogdog, mongoose, antelopefoxes, skunks, raccoons,
insectivorous batsdog, vampire batsMiddleAsiaAfricaEastN AmericaS
AmericaKERENTANAN HEWAN THD RABIES VIRUSSANGAT
TINGGITINGGISEDANGRENDAHRUBAHHAMSTERANJINGTUPAICOYOTEMUSANGLEMBUSERIGALARAKUNDOMBAANJINGHUTANKUCINGKAMBINGKELELAWARKUDAKELINCIPRIMATA
BUKANMANUSIAWABAH RABIESINDONESIA 2004-2008 15.000 DIGIGITBADUNG,
BALI VAKSIN 20.000 ANJINGTH 2008 14.106 ORANG: 9565 DIBERI VAKSIN
DANOBAT; 85 RABIESBALI 1700 ORANGPENYEBAB: POPULASI ANJING TDK
TERKENDALI KRN LEMAHNYA SISTEM DETEKSI DINI DAN EVALUASI PERIODIK
SURVEY SEROLOGI ANTIBODI DARI HEWAN SUMBER PENULARAN HARUSNYA
DILAKUKAN PERIODIKPathogenesisThe commonest mode of transmission in
man is by the biteofarabid animal, usually adog.Rabiesisan
acuteinfection 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 theSchwann
cells.Terminally, there is widespread CNS involvement but
fewneuronsinfectedwiththevirusshowstructuralabnormalities. The
nature of the profound disorder is stillnot understood.Viral
cycleViral cycleViral PathogenesisPATOGENESA & PATOLOGIVIRUS
OTOT/JAR IKAT (BKBG BIAK) , KADANG TANPAREPLIKASI 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, KORNEAVIRUS BLM PERNAH
DIISOLASI DARI DARAH PASIENTERINFEKSIVIRUS MEMBENTUK BADAN INKLUSI
INTRASITOPLASMA,ASIDOFILIK PD SEL SARAF TERINFEKSI BADAN
NEGRIPATOGENESA & PATOLOGIKERENTANAN & MASA INKUBASI
TERGANTUNG :UMUR PASIENLATAR BELAKANG GENETIK STATUS IMMUNSTRAIN
VIRUS PATOGENITAS VIRUSJUMLAH INOKULUM JUMLAH VIRUS YANG MASUK
BERATNYA LASERASI DALAM DAN PARAHNYA LUKABEKAS GIGITAN, JUMLAH LUKA
GIGITAN, JUMLAH SYARAF DISEKITAR GIGITANJARAK DARI PORT DTRY SSP
(LOKASI LUKA)GIGITAN DI KEPALA/WAJAH MASA INKUBASI PENDEK, SERANGAN
TINGGIGIGITAN PADA KAKI KEMATIAN RENDAHGEJALA KLINISENSEFALITIS
AKUT, FULMINANT, FATALMASA 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 TAHUNFASE KLINIS FASE
PRODOMAL PENDEKFASE NEUROLOGI AKUT KOMAGEJALA KLINISFASE PRODOMAL
PENDEK :2-10 HARIMALAISE, ANOREXIA, NYERI KEPALA, FOTOPOBIA, MUAL,
MUNTAH NYERI TENGGOROKAN, DEMAMFASE 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 PERNAFASANRABIES PARALITIK TERJADI SEKITAR 20% PASIEN
AKIBATTERINFEKSI VIRUS RABIES KELELAWARBBRP BTHN 30 HARI, TP JARANG
YANG DPT SEMBUH & BTAHANHIDUPGEJALA 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, KEJANG2DALAM WKT SINGKAT, LUMPUH TDK DAPAT MENELAN,
HIPERSALIVASI BENTUK ASYMPTOMATIS: TANPA GEJALA, TIBA-TIBA MATIDumb
RabiesDumb Rabies, manifested as depresion and an attempt at
self-imposed isolationGEJALA PADA MANUSIA NAFSU MAKAN HILANG, SAKIT
KEPALA, TIDAKBISA 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 KELUMPUHANBIASANYA
MENINGGAL DALAM WAKTU 4-6 HR SETELAH GEJALA KLINIS PERTAMA
TIMBULGEJALA PADA MANUSIA KALAU DIGIGIT DEKAT LEHER/KEPALA AKUT:
DEMAM TINGGI KEJANG2 OTOT MULUT BERBUSA FOTOPHOBIA KESADARAN
MENURUN BERTERIAK-TERIAKHuman rabiesHospitalized human rabies, who
was restrained while bedriddenHuman rabiesHospitalized human rabies
victim in restrainsLaboratory DiagnosisHistopathology - 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 intoinfant
mice.Because of the difficulties involved, this is rarely offeredby
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.DIAGNOSA LABORATORIUMANTIGEN
RABIES/ASAM NUKLEATIMMUNOFLUORESCENS, PCR (JAR OTAK/KORNEA ISOLASI
VIRUSINTRACEREBRAL PADA TIKUS YG BLM DISAPIH ENSEFALITIS &
KEMATIANSEROLOGIIMMUNOFLUORESCENS, TES NtOBSERVASI HEWANSELAMA 10
HARI PADA HEWAN RESERVOARDiagnosisofRabiesNegri Body in neuron
cell(source: CDC)Positive DFA test (Source: CDCCharacteristic Negri
BodiesHistopathologic features of rabies, brain. Characteristic
Negri Bodies are present within a Purkinye cell of the cerebellum;
patient died of rabiesManagement and PreventionPre-exposure
prophylaxis - Inactivated rabies vaccine may beadministered 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 bekilledand
examined.Theessentialcomponentsofpostexposureprophylaxis are the
local treatment of wounds and active and passiveimmunization.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.Postexposure ProphylaxisWound 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.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 INFEKSIPENANGGULANGAN KASUS
AKUT:VAKSIN EFEK SAMPING: MENINGITIS + GJLSEPERTI RABIESYODIUM TDK
MEMBANTU KRN VIRUS SDH MSKIg ANTI RABIES CEGAH VIRUS TDK MENYEBAR
KE SYARAF OTAKISOLASI PENDERITA BISA MENULARKAN OBAT TDK ADA,
TERAPI SYMPTOM: ANTIKEJANG, OBAT CEGAH INFEKSI SEKUNDER,OBAT
PENENANGRabies VaccinesThe vaccines which are available for humans
are present are inactivated whole virus vaccines.Nervous Tissue
Preparation e.g. Semple Vaccine - associated with the
rarecomplication 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.IMMUNITAS & PENCEGAHANVAKSINASI :VAKSIN SEL DIPLOID
MANUSIA (HDCV) VAKSIN RABIES TERABSORPSI (RVA)VAKSI SEL EMBRIO AYAM
DIMURNIKAN (PCEC)VAKSIN JARINGAN SARAF VAKSIN EMBRIO BEBEK VIRUS
HIDUP DILEMAHKANTIPE ANTIBODI RABIES :Ig RABIES MANUSIA (HRIG)
SERUM ANTIRABIES KUDAIMMUNITAS & PENCEGAHANPENCEGAHAN SEBELUM
PEMAPARAN :VAKSINASI PADA INDIVIDU BERESIKO TINGGIPENCEGAHAN
SETELAH PEMAPARAN :PENATALAKSANAAN & PENGENDALIAN :Control of
Rabies Urban - canine rabies accounts for more than 99% of all
humanrabies. Control measures against canine rabies include; stray
dog control. Vaccination of dogs quarantine of imported
animalsWildlife - 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.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
anjingSkor LARAT LARAT: nama titik terluar NKRI, yangberbatasan
langsung dengan Samudra HindiaProbability/Peluang kejadian Rabies
pada pasien gigitan anjing saat KLB Rumus11+e-(F)Skor LARATF = 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
epidemiologiSistem skoring prediksi rabies pada pasiengigitan
anjing saat KLB RabiesNoVariasiKategoriSkor1Selisih waktu gigitan
anjing< 2 bulan 2 bulan202Lokasi luka gigitan anjingKepala,
wajah, leher, dada, punggungLengan, tangan, perut, tungkai,
kaki103Karakteristik anjing (ada 7 karakteristik)Dominan Rabies ( 4
sifat)Tidak dominan Rabies (< 4 sifat)304Akibat kematian
anjingAnjing mati sendiri, atau anjing dibunuh namun diperoleh
informasi bahwa anjing tersebut mati telah digigit anjing lain yang
mati sendiri Anjing dibunuh, tidak mati, tidak tahu30Skor
maksimumSkor minimum90Analisis sensitivitas danspesifisitas pada
ROC curve, skor 5 memberikan prediksi Rabiessehingga perlu mendapat
prioritas vaksinasi di saat KLB
