Oleh :

Dr.dr. Efrida Warganegara, M.Kes., Sp.MK

 Arthropod Borne Viruses
Arthropod Borne virus disingkat menjadi ARBO VIRUS
Yang penting pada manusia : Togaviridae dan Flaviviridae 
yang banyak mirip dengan Bunyaviridae dan Reoviridae
Reservoir alami dari virus ini adalah : hewan, burung, reptil
 pada mana mereka ditransmisikan oleh gigitan arthropod
penghisap darah, misal : Nyamuk, sandfly, atau Ticks
Manusia terinfeksi hanya jika mereka masuk kedalam area
dimana mereka ada dan mendapat gigitan oleh arthropod
yang terinfeksi
Infeksi sering inapparent atau trivial, tapi beberapa virus ini
dapat menyebabkan penyakit sangat berat dan bahkan
fatal, antara lain :
- Penyakit panas, sering dengan rash dan arthritis
- Infeksi sistem syaraf pusat
- Hemorrhagic fever
1. Japanese encephalitis virus, St.Louis
encephalitis virus, Powassan, & tick-borne
encephalitis viruses  Encephalitis

2. Dengue virus  Febrile illness with rash &

sometimes Hemorrhagic fever

3. Other diseases : Kyasanur Forest disease

virus, hemorrhagic fever with hepatitis,
yellow fever virus.
 Dengue Fever
Dengue Fever is a mosquito-borne viral
disease, also known as “break-bone
fever”, because it causes severe joint
and muscle pain

The disease is found in many tropical

areas and is now endemic in more than
100 countries worldwide.
It is the most common vector-borne viral
disease in the world
 Dengue Fever – causative agent
Dengue fever is caused ny a single-
stranded RNA Virus of the Flavivirus
family
There are four closely related serotype of
the virus : DENV-1, DENV-2, DENV-3,
DENV-4, which are transmitted by the
bite of an infected mosquito of the
Aedes family.
The most common vector is Aedes
aegyptie, the same species that carries
Yellow fever
 Dengue Fever – causative agent
Another important vector of dengue
virusses is Aedes albocpitus, the Asian
tiger mosquito, now spreading
worldwide.
This vector also transmits the dengue-
like viral disease chikungunya.
Both of these mosquito species feed only
during the day.
Found at 1779.
VIRAL CHARACTERISTIC :
Survive at t 8 C for 5 years
4 type :
DENV-1, DENV-2, DENV-3, DENV-4
E envelope proteins as specific antigenic.

The major protein in dengue

virus, called 'E' for envelope protein
(color-coded blue, green and yellow),
protective shell around the virus.
 Dengue Fever – pathogenesis
When an infected mosquito feeds on a human
host, dengue viruses are injected into the bite
wound, where they infect keratinocytes and
epidermal dendritic cells.
Some of these cells migrate to the lymph nodes,
where monocytes and macrophage are
recruited and also become infected
Dengue viruses multiply in the macrophages
and are then dessiminated systemically in
these cells
Humoral and Cell-mediated immune response
clear the viruses
 Dengue Fever – pathogenesis
The infected macrophage produce pro-inflamatory
cytokines, resulting in a cytokine storm.
This, along with activated complement and
cytokines released by memory T-cells, causes
changes in vascular permeability, leading to
plasma leakage, that may result in respiratory
distress and dehydration.
Capillaries become fragile, resulting in the
observed hemorrhages (petechiae etc). Infected
macrophages die and release toxic products that
causes blood clotting and DIC
Leucopeni occurs, blood pressure drops,
sometimes to life-threatenin levelsg
 DENGUE VIRUS :
-Reservoir : Aedes aegypti & albopictus

Skin cell Perivacsular oedema .

capillary endothelium Infiltration of mononuclear cell--
Hyporoteinaemia
hypertrophy & hyperplasi Dehydration  hypovolemia 
capillary wall Shock.

increase permeability Shock  heart works harder 

 transport O2 < 
Extravasage Anoxia  tissue acidosis
& hyper-potasiumemia
death †
Incubation period between 1 - 7 days
 Dengue Fever – epidemiology
Dengue is an emerging disease and the
fastest spreading mosquito-borne viral
disease in the world
It is found in mostly tropical and
subtropic regions that have high
rainfall and plenty of fresh water,
conditions that aid in disease
development because the mosquito
vector breeds in standing water
Clinical appearance :
1. Classical Dengue syndrome (CDS = SDK) :
- Not fatal.
- Children : fever, weak, anorexia, skin rash
 heal.
-Adult : saddle-like fever always followed
headache, myalgia and
bone ache  fever   rash.

2. Dengue Hemorrhagic Fever (DHF) :

- Firstly like CDS  3-4 days hemorrhage of :
nose, gingival, conjunctiva, vagina, &
hemetemesis, melena
- Can healing but death is more frequent.
3. Dengue Shock Syndrome (DSS) :
-Mortality rate >>
-WITH OR WITHOUT bleeding.

Symptoms :
i. Firstly as CDS
ii. Day II – IV : epigastrium palpation
painful
iii. Patient nervous  death.
 Diagnosis
• Diagnosis DBD dengan kriteria WHO (1986)
– Klinis :
• Demam tinggi mendadak, tanpa sebab jelas,
berlangsung terus menerus selama 2-7 hari.
• Terdapat menifestasi perdarahan termasuk uji
torniquet positif, petikie, ekimosis, epistaksis,
perdarahan gusi, hematemesis dan atau
melena.
• Pembesaran hati
• Syok, ditandai denan nadi cepat, lamah serta
penurunan tekanan nadi, hipotensi kaki tangan
dingin, kulit lembab dan gelisah
– Laboratorium :
• Trombositopenia (100.000/mm3 atau kurang)
• Hemokonsentrasi
 Diagnosis........
• Hemokonsentrasi  akibat
permeabilitas kapiler dgn manifestasi :
– Peningkatan Ht > 20% dibandingkan
standar sesuai umur dan jeis kelamin.
– Penurunan Ht > 20% atau lebih setelah
mendapat pengobatan cairan
– Perembesan plasma yaitu efusi pleura,
asites atau proteinemia.
Diagnosis:

A. Isolation :
- Spec : - blood (first 3 days illness)  intra
cerebral inoculation to mouse baby
or to salivary gland A. aegypti
- Isolation is difficult  diagnosis
established by serologic.

B. Serologic :
- To look at increase of dengue titer with Nt &
HI test
Strategy of Management :
Treatment:
1. Not yet present specific treatment.
2. Don’t let to become shock.
3. We have several action must be done :
- Blood transfusion if Hb <<
- If Hb N but Ht high  plasma transfusion.
- Heparin if heavy DHF.
- Adrenalin & Isoprenosin  to  shock &
death.
Control (vector control) :
1. Fogging : malathion
2. To rinse. to close & to burry (3 M).
3. Community health education.
 Pengobatan Demam Dengue
• Tirah baring selama demam
• Antipiretik
• anjuran parasetamol
• tidak dianjurkan:asetosal, ibuprofen
• Analgesik bila perlu (anak besar)
• Cairan & elektrolit oral
• jus buah, sirup,susu
• oralit, pocari sweat
• Monitor
• suhu,
• trombosit
Dr.dr. Efrida Warganegara, M.Kes., Sp.MK
 INTRODUCTION
The largest & most complex of viruses known
Smallpox first appeared in China and the Far East at least
2000 years ago.
The family encompasses a large group of agents,
morphologically similar,
share a common nucleoprotein
antigen
The group includes variola virus
etiologic agent of smallpox,
disease has most affected humans
throughout the world
recorded history until elimination in 1977
 INTRODUCTION
Eradication & vaccination all over the world started
by WHO (1967)
Smallpox has been declared eradicated from the
world (May 1980) after an extensive campaign
coordinated by WHO
Vaccinia virus is under intensive study as a vector
for introducing active immunizing genes as live-
virus vaccines for a variety of viral diseases of
humans & domestic animals
 POXVIRUSES CAUSING DISEASE IN HUMANS
Genus Virus Primary Disease
host
Orthopoxvirus Variola Humans Small pox (now extinct)
Vaccinia Humans Localized lesion, used
for smallpox vaccination
Buffalopox Water buffalo Human infection rare, local
Monkeypox Monkeys Human infection rare,general
Cowpox Cows Human infection rare, local
Parapoxvirus Orf Sheep Human infection rare, local
Pseudocowpox Cows Milkers’ nodes
Bovine papular Cows
stomatitis
Molluscipoxvirus Molluscum Humans Many benign skin nodules
contagiosum
Yatapoxvirus Tanapox Monkeys Human infection rare, local
Yabapox Monkeys Human infection very rare,
accidental, localized skin tumor
 VIRUS REPLICATION
 Multiplication cycle takes place in the
cytoplasm, in which they form inclusion
bodies
 Nuclear factors involved in transcription and
virion assembly
 Propagation in the laboratory :
most poxviruses can be propagated on
the chorioallantoic membrane of the 10 –
12 days old chick embryo, form
circumscribed pocks,
Ø 2 - 3 mm or in cell cultures
 Molluscum contagiosum virus has not so far
been grown in the laboratory
VIRUS REPLICATION
 POXVIRUS INFECTIONS IN HUMANS :
VACCINIA & VARIOLA
Control & eradication of smallpox :
 Edward Jenner (1798) introduced
vaccination with live cowpox virus
 In 1967 WHO introduced a worldwide
campaign to eradicate smallpox
 The last Asiatic case occurred in
Bangladesh (1975)
 The last natural victim was diagnosed
in Somalia (1977)
The main reasons for outstanding
success of vaccination & eradication ;

 The vaccine was easily

prepared, stable, safe
and effective
 It could be given simply
by personnel in the field
 Humans are the only
natural host
 Only I type of smallpox
virus
Comparison of vaccinia & variola virus :

Vaccinia virus : Variola virus :

Used for smallpox
vaccine
Has a broad host Has narow host range
range Nucleotide sequences
Nucleotide sequences 186 kb
192 kb
PATHOGENESIS & PATHOLOGY OF
SMALLPOX
Portal of entry : mucous membranes of
respiratory tract
1. Primary multiplication in lymphoid
tissue draining the site of entry
2. Transient viremia & infection of RE
cells throughout the body
3. Secondary phase of multiplication
4. Secondary & more intense viremia
5. Clinical disease
Smallpox was transmitted by respiratory route
from lesions in the respiratory tract of patients
in the early stage of the disease.
During the 12 day incubation period, the virus
was distributed initially to the internal organs
and then to the skin.
Variola major caused severe infections with
20-50% mortality, variola minor with <1%
mortality.
Management of outbreaks depended on the
isolation of infected individuals and the
vaccination of close contacts.
The vaccine was highly effective. If given
during the incubation period, it either
prevented or reduced the severity of clinical
symptoms.
At least 9 different poxviruses
cause disease in humans,
but variola virus (VV) and
vaccinia are the best known.
VV strains are divided into
variola major (25-30%
fatalities) and variola minor
(same symptoms but less
than 1% death rate).
"Variolation" = the
administration of material
from known smallpox cases
(hopefully variola minor!!!)
to protect recipients -
practiced for at least 1000
years (Chinese) but risky -
Jenner was nearly killed by
variolation in 1756!
 IMMUNITY
An attack of smallpox complete protection
against re-infection
Vaccination with vaccinia induced
immunity against variola virus at least 5
years & sometimes longer
Neonates of vaccinated, immune mother
receive maternal antibody
transplacentally, persists for several
months.
After that time, artificial immunity can be
produced by vaccination