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TOGAVIRIDAE DAN

FLAVIRIDAE
KMB 441

Dr. Edhie Djohan Utama, SpMK


Bagian Mikrobiologi
FK USU Medan

TOGAVIRIDAE DAN FLAVIRIDAE

YANG TERMASUK KEDALAM ARBOVIRUS


TOGAVIRIDAE (genus Alphavirus & Rubella virus)
FLAVIRIDAE (genus Flavivirus)
BUNYAVIRIDAE (genus Bunyavirus, genus
Phlebovirus, genus Nairovirus dan genus Hantavirus)

REOVIRIDAE (genus Orbivirus)


RHABDOVIRIDAE (genus Vesiculovirus)
ARENAVIRIDAE (genus Arenavirus)
FILOVIRIDAE (Marburg & Ebola virus)

TOGAVIRIDAE & FLAVIVIRIDAE

Famili Togaviridae mula-mula mencakup genus : alphavirus


flavivirus rubivirus
Penggolongan berdasarkan :
Ukurannya
RNA rantai tunggal tak bersegment dan berfungsi sebagai
mRNA
Kemampuan bereplikasi didalam nyamuk
Kemudian ditemukan bahwa Flavivirus berbeda dari
Togavirus, yaitu berbeda dalam :
Ukuran Flavivirus yg lebih kecil (40 50 nm)
Berbeda dlm urutan gen dan strategi replikasinya.
Sejak 1984 masing2 jadi famili tersendiri :
Togaviridae dan
Flaviviridae

DUA GOLONGAN TOGAVIRUS :

Kelompok ARBO-virus :
Infeksinya melalui nyamuk (culex dan Aedes) serta
kutu ( tick),

kebanyakan menyebabkan encephalitis, demam


berdarah dan yellow fever.

ARBO-virus ini bisa berkembang didalam arthropoda


pengisap darah (hematophagous) dan merupakan vector
penyakit.

Kelompok non-ARBO-virus : Rubella virus dari


Rubivirus. (Rubella = merah kecil) di ketemukan oleh
Norman Mc Alister (Dokter German) tahun 1941.

Structure Alphavirus
Virions are spherical, 60 to 70 nm in diameter, icosahedral
nucleocapsid a lipid-protein envelope. Alphavirus RNA is
a single 42S strand of approximately 4 x 106 daltons.
The alphavirus envelope consists of a lipid bilayer derived
from the host cell plasma membrane and contains two viral
glycoproteins (E1 and E2) of molecular weights of 48,000
to 52,000 daltons.
A small third protein (E3) of molecular weight 10,000 to
12,000 daltons remains virion-associated in Semliki Forest
virus but is dispatched as a soluble protein in most other
alphaviruses.

PATHOGENESIS OF ALPHAVIRUS

ALPHAVIRUS TRANSMISSION

TOGAVIRIDAE (Genus Alphavirus)

TOGAVIRIDAE : spherical, 70 nm, ssRNA, mempunyai envelope, ditularkan melalui nyamuk. (ARBOVIRUS) Menyebabkan penyakit encephalitis.
Chikungunya
Eastern equine encephalitis
Mayaro
ONyongnyong
Ross River
Semliki Forest
Sindbis
Western Equine Encephalitis

TOGAVIRUS YANG ARBOVIRUS :


Anggota Alphavirus Vector dan Hospes

Virus

Vector

Chikungunya
ONyongnyong
EasterAquine Enc.
Mayaro

Aedes
monyet-baboon
Anopheles ??
Aedes
burung
nyamuk &
marmoset, priHaemagogus mata lainnya
Aedes ny ll burung
Aedes ll
burung
Aedes, Culex pengerat, ternak
Culex &
burung
Culiseta

Sindbis
Semliki forest
Ross River
Western equine enc.

Hospes

CHIKUNGUNYA

Terdapat di :
Afrika
Azia Tenggara
Philipina dan India

Vektornya : nyamuk
Hospes : monyet dan baboon
Menimbulkan gejala

demam,
pendarahan,
arthritis

TOGAVIRIDAE
(YANG NONARBOVIRUS)

RUBELLA VIRUS :
Penyebab penyakit measles / cacar German.

Disebut juga 3 day measles


Demam akut dengan skin rash dan lymph- adenopathy
daerah auricular dan suboccipital pada anak anak atau
dewasa muda
Infeksi pada waktu hamil menyebabkan kelainan kongenital
yang serius (congenital Rubella syndrome)

Clinical Manifestations
Postnatal rubella (German measles) is a generally mild, selflimited illness characterized by rash, lymphadenopathy, and
low-grade fever. However, congenital rubella may cause a
number of anomalies, depending on the organ system
involved and gestational age.

Structure Rubella virus

Rubella virus is a spherical, 40- to 80-nm,


positive-sense, single-stranded RNA virus with
spike-like, hemagglutinin-containing surface
projections. An electron-dense 30 to 35 nm core
is surrounded by a lipoprotein envelope.

Classification and Antigenic Types

Rubella virus is the sole member of the genus


Rubivirus in the family Togaviridae. Only one
serotype has been identified. It contains three
major structural polypeptides.

Pathogenesis and Host Defenses

The disease is transmitted via direct or droplet


contact with respiratory secretions. Rubella virus
multiplies in cells of the respiratory system; this is
followed by viremic spread to target organs.
Congenital infection is transmitted transplacentally.

Neutralizing and hemagglutination-inhibiting


antibodies and cell-mediated immunity develop
promptly. Reinfection (usually asymptomatic) can
occur.

MENYEBABKAN KELAINAN KONGENITAL


Kelainan kongenital jantung :
Patent ductus arteriosus pulmonary stenosis
ventricular septal defect )
Kelainan kongenital pada mata :
Total / partial blindness (catarract, glaucoma,
chorioretinitis)
Kelainan pendengaran : neurosensory deafness
Kelainan mental dan pertumbuhan
hepatosplenomegaly, thrombocytopenia
purpura, osteitis, meningoencephalitis

KELAINAN KONGENITAL :

Infeksi oleh Rubella pada ibu menyebabkan infeksi


pada placenta dan fetus
the virus produces chromosomal abnormalities, slows
cellular growth rates, and causes cell lysis and death in
some cell types; these effects appear capable of
producing the characteristic abnormalities of cell
structure and function
Infeksi pada 1-2 bulan kehamilan menyebabkan
abnormalitas pada 40-60% dari fetus
Infeksi pada 3 bulan kehamilan
abnormalitas
30-35% dari fetus
Infeksi pada 4 bulan kehamilan
abnormalitas
4% dari fetus.

DIAGNOSIS INFEKSI RUBELLA


Diagnosis secara klinis
Diagnosis Laboratorium
Isolasi dan identifikasi virus
Memakan waktu dan tidak sensitip
Nasopharyngeal swab
Throat swab
Serology
HI test
CF test
ELISA test : IgM dan IgG

FLAVIVIRUS

Flavi = kuning
Dulu digolongkan kedalam Togaviridae
Arbovirus (Arthropod Borne Virus)
Flavivirus berukuran kecil (40 nm), berbeda dalam
morfogenesis dan berbeda dalam struktur genomnya dari
Togavirus.
Protein penyusun virion = 3protein :

C (kapsid), E (selubung) dan M (membran)

Yang teriinfeksi sering menyebabkan encephalitis, dasarnya


adalah neurotrofik khususnya pd binatang pengerat

SPEKTRUM PENYAKIT
60 anggota flavivirus diketahui dapat menyebabkan penyakit pd manusia.
Spektrum penyakit sangat luas secara umum dibagi atas 3 kelompok :
1. Pola viseromorfik (demam-berdarah)
2. Pola pantamorfik ( demam)
3. neuromorfik (gejala ensefasilitis)
Diagnose :
1. isolasi dan identifikasi virus
2. pemeriksaan serologi (Elisa-netralisasi)
3. PCR (Polymerase chain reaction)

Flaviviridae
Flavivirus)
(Genus
Spherical, 40 nm, RNA, envelope

Dengue hemorrhagic fever (DHF)

Brazillian encephalitis
Japanese B Encephalitis
Kyasanur Forest Disease
Murray Valley Encephalitis
Russian Spring-Summer Encephalitis
St. Louis Encep[halitis
Tick-borne Encephalitis
West Nile Fever
Virus-virus Yellow Fever

PATHOGENEISIS OF FLAVIVIRUS

DENGUE
VIRUS
Virus Dengue termasuk kedalam Flavivrus

dan

adalah ARBO VIRUS group B


Infeksi melalui gigitan nyamuk Aedes aeqypti dan
berkembang juga pada A.albopictus (hutan)
Dikenal dengan 4 serotype
Secara antigenic punya persamaan dengan virus
yellow fever
Gejala Klinis : (Breakborne fever)
demam, sakit otot dan sendi, lymphadenopathy dan
skin rash, serta thrombocytopenia
Sembuh beberapa minggu kemudian dan pada
anak anak bisa demam 1-3 hari saja

DENGUE VIRUSES
Dengue viruses of all four serotypes cause three distinct
syndromes : classic dengue fever, dengue hemorrhagic
fever, and dengue shock syndrome.
Although caused by the same viruses, dengue and dengue
hemorrhagic fever are pathogenetically, clinically, and
epidemiologically distinct.
Dengue viruses appear to replicate in macrophages at the
site of the mosquito bite, in regional lymph nodes, and
then throughout the reticuloendothelial system.
Viremia is concurrent with clinical illness. Virus is present
in the serum and in association with circulating
monocytes. Severe leukopenia often is present.

Dengue hemorrhagic
Dengue hemorrhagic fever results from
additional pathogenetic processes not
present in classical dengue fever; the most
important of which are :
1.Diffuse

capillary leak with hemoconcentration,


2.Thrombocytopenia, and
3.Disseminated intravascular coagulation.

Immunopathologic mechanisms

It has been postulated that cross-reacting antibodies from


a previous dengue infection or maternal anti-dengue
antibodies in infants enhance the entry of virus into
macrophages
The increased viral replication in the macrophages then
contributes to the complement activation, vascular
permeability, and clotting abnormalities observed in
patients, through the release of products from infected
macrophages.
It is speculated that T cells exacerbate the antibodyenhanced destructive cascade, as they vigorously respond
to (and then destroy) antigen-presenting cells, with
concomitant release of cytokines by both T cells and
damaged macrophages

GEJALA KLINIS DENGUE


Serangan demam tiba tiba atau ada gejala
prodromal malaise, keringat dingin, sakit kepala
Rasa sakit pada punggung, persendian, otot dan
bola mata
Suhu tubuh normal kembali setelah demam 5-6
hari dan kemudian suhu normal 3 hari lalu
demam kembali (saddle-back form fever)
Skin rash (maculopapular / scarlatiniform bisa
terlihat pada hari ke-3-4 selama 24-72 jam, lalu
rash berkurang-meredup dan desquamasi

CLINICAL SYMPTOMS DENGUE FEVER


Dengue fever is characterized by sudden onset of
systemic toxicity, fever, headache, vomiting, and severe
myalgia or bone pain of escalating intensity.
Either coincident with or following remittance of fever on
days 3 to 5 of the illness, there appears a maculopapular or
morbilliform rash on the trunk which spreads to the limbs
and face.
This phase of the illness is often accompanied by
recrudescence of fever, lymphadenopathy, granulocytopenia,
and thrombocytopenia. Minor mucocutaneous bleeding is
occasionally manifested by petechiae, epistaxis,
menorrhagia, and a positive tourniquet test. Dengue fever
lasts 3 to 9 days, is self-limiting, and is rarely associated
with serious sequelae.

DENGUE HAEMORRHAGIC FEVER .


In contrast, the clinical course of dengue
hemorrhagic fever is characterized by an initial
stage of fever, rash, and anorexia (lasting 3 to 5
days) followed by a shock phase in which
hepatomegaly, hypotension, and a hemorrhagic
diathesis occur.
Complement activation and thrombocytopenia
typically take place at the onset of the shock phase
and reverse spontaneously after a period that
ranges from hours to a few days.

Dengue Shock Syndrome

In dengue shock syndrome, the decreased


plasma volume which results from increased
vascular permeability causes clinical shock
that, if uncorrected, may lead to acidosis,
hyperkalemia, and death.

Ninety percent of dengue hemorrhagic fever


cases occur in children experiencing multiple
infections with dengue.

DENGUE HAEMORRHAGIC
FEVER (mortalitas 5-10%)
Bisa terjadi gejala gejala yang berat :
Hypoproteinaemia
Thrombocytopenia
Bleeding time >>
Prothrombine time >>
Dengue shock syndrome
shock
hemoconcentrasi

NYAMUK AEDES AEGYPTI


Nyamuk betina mengisap darah pasien yang
viremia
Dalam 8-14 hari kemudian nyamuk bisa
menyebarkan virus Dengue
Gejala klinis muncul setelah 2-15 hari digigit
nyamuk
Nyamuk tersebut akan infective selama 1-3
bulan atau lebih

PENYAKIT PENYAKIT
HEMORRHAGIC FEVER :
DENGUE HEMORRHAGIC FEVER (DHF)
RODENT-BORNE HEMORRHAGIC FEVER
(Hantaan virus)
EBOLA HEMORRHAGIC FEVER (Marburg
& Ebola virus Filoviridae)
SOUTH AFRICAN HEMORRHAGIC
FEVER (Junin & Machupo virus)

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