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DENGUE INFECTION

Gatoet Ismanoe, MD, FINASIM


Division of Tropical and Infectious Diseases
Department of Internal Medicine
Brawijaya University / Saiful Anwar General
Hospital Malang

Introduction
Dengue is the most common mosquito-borne
infection
100 million infections worldwide per year
the dramatic expansion fueled by ->
urbanization, increased population density, air
travel, limited resources for dengue prevention.
A study of pregnant woman from Thailand
indicated -> 94.7% had serological evidence of
previous dengue infection.

Dengue infection
First recognized in 1950s

Flaviviridae (70 viruses)


4 serotypes
DEN-1, DEN-2, DEN-3, DEN-4
Mosquito-borne infection

Aedes albopictus (slow-moving)


Aedes aegypti (fast-moving)

Dengue Virus

Single-stranded RNA virus


Causes dengue hemorrhagic fever
Transmitted by mosquitoes (Aedes aegypti)
Serotypes (DEN-1, 2, 3, 4)

Countries/areas at risk of dengue


transmission, 2008

Average annual number of dengue fever (DF) and dengue haemorrhagic


fever (DHF) cases
reported to WHO, and of countries reporting dengue, 19552007

Global Burden
Two fifths of the world (2.5 billion people)
population are at risks
50-100 million people are infected every
year
250,000 people progress to dengue
hemorrhagic fever each year
25,000 death each year
Missing data on non-hospitalised and less
severe cases

Problems
Leading cause of serious illness and death
among children in some Asian countries
Increase incidence of dengue infection in
adult
Pregnant women are more and more
susceptible
Intensive mosquito-control programme
resulted in children with non-immune to
dengue

immune systems respective responses

Sel Target
Monosit
Makrofag
Sel Kupffer

Virus DEN

Komplemen

Interferon
Interferon

Hiperaktifitas
komplemen

Pelebaran celah Endotel


Pe Permeabilitas

Pe Sekresi Histamin

Virus DEN
Ensim PLA 2

Makrofag
Metabolisme
As Arakhidonat

Jalur Siklooksigenase
Leokotrien
Protasiklin
Tromboksan
Prostaglandin E-2

Membuka Celah
Endotel kapiler

Virus DEN
Aktifasi Gen
NF-kB

Makrofag

Produksi & Sekresi


Sitokin Proinflamatori

IL-I
Malfungsi Endotel
IL-I 6
TNF -> Destruksi Endotel

Plasma Leakage

Virus DEN

Makrofag

Sintesis NO

Pe Kelenturan
Dinding Kapiler
ROS

Plasma Leakage

Clinical manifestation
Asymptomatic
Dengue fever
Dengue hemorrhagic fever
Dengue shock syndrome

Dengue fever
Acute febrile illness with two or more of the
following
Headache, retro-orbital pain, myalgia,
arthralgia, rash, hemorrhagic manifestation,
leukopenia
Lab for confirmation
Isolation of dengue virus, fourfold rising in
reciprocal IgG or IgM, PCR (genomic
sequence), immunostaining (dengue antigen)

Dengue hemorrhagic fever


Fever (last 2-7 days), occasionally biphasic
Hemorrhagic tendency
Tourniquet test, petechiae, bleeding from mucosa
Thrombocytopenia (< 100,000 cell/mm3)
Evidence of plasma leakage
Hct increase >20%, Hct drop >20% after
volume replacement, pleural effusion, ascites,
hypoproteinaemia

Dengue shock syndrome


Evidence of circulatory failure
Narrow pulse pressure < 20
mmHg
Hypotension
Rapid and weak pulse
Cold, calmy skin, restlessness

Time course of clinical signs and


symptoms

Febrile, critical and recovery phases in dengue


1 Febrile phase

Dehydration; high fever may cause neurological


disturbances and febrile seizures in young
children

2 Critical phase

Shock from plasma leakage; severe haemorrhage; organ


impairment

3 Recovery phase

Hypervolaemia (only if intravenous fluid therapy has been


excessive and/or has extended into this period)

Early Diagnosis :simple clinical & lab.


Tourniquet test
CBC PPV = 70-80%
Tourniquet test positive + leucopenia*
= Dengue infection
*Leucopenia = wbc 5,000 cells/cumm

At least day 3 of fever


CBC everyday if possible
Close follow up until 24 hours of
defervescence

Tourniquet Test
Fever day 1
50%
Fever day 2
70%
Fever day 3 > 90%
False negative TT
Obese patients
Thin patients
Not good technique
During shock

Sensitivity in the febrile phase


(First few days of fever)

PCR: >95% - expensive, not available


in most places
ELISA : 60% on the day of shock
30-40% one day before shock
100% one day after shock
NS1Ag: 60-70%

WBC 5,000 cells/cumm


Early diagnosis
Indicates: no fever within the next 24
hours
If DHF :
Entering critical stage
Beginning of plasma leakage
If severe : aware/ prevent
shock? Is possible

Prolonged shock
> 10 hours untreated - Death!!!
> 4 hours untreated
Liver failure- prognosis 50%
Liver + Renal failure prognosis
10%
3 organs failure (+respiratory
failure) Prognosis is a miracle!!!

Indications for admission


Shock
Platelet 100,000 cells/cumm. c no
good clinical conditions; poor appetite..
High risk patients: Obese, infants,
bleeding, underlying diseases,
consciousness change
No care-taker
Live far away
Mass-media families

Warning signs of shock


Clinical deterioration/ not improve when no
fever/ low
grade fever
Abdominal pain
Vomiting
Restless, shortness of breath, persistent crying
in infants
Sweating, cold clamy skin
Behavior change, drowsy
No urine 4 - 6 hours

A stepwise approach to the management of dengue

Algorithm for fluid management in


compensated shock

Algorithm for fluid management in


hypotensive shock

THANK YOU
Lucerne, Swiss

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