Dengue Infection

Dengue fever is an acute febrile arboviral

disease affecting the tropical and subtropical
regions of the world.

It affects up to 100 million people each year,

with 500.000 cases of DHF and DSS and
around 30.000 deaths, mostly among
children.
Dengue virus is a ss-RNA virus with a genome
of 10.7 kb in length, enveloped, spherical 50
nm in size.
There are four antigenically distinct DV
serotypes, DENV-1, DENV-2, DENV-3 and
DENV-4 and each serotype contains four to
five genotypes on the basis of their genomic
sequences.
Infection with one serotype leads to
lifelong protection against homotypic
reinfection, do not confer cross
immune protection to each other.
Studies have shown that heterotypic
secondary infection is associated with higher
risk of contracting DHF and DSS possibly
through :
Antibody-dependent enhancement
Original antigenic sin
Cytokine storm, or
Autoimmune response
Viremic individuals are the main
source of infectious virus. Virus is
transmitted following mosquito bites
of these viremic individuals.
Transmision
DENV is transmitted through a human-
mosquito cycle with the aid of Aedes
aegypti and Ae. Albopictus mosquito
vectors.
The liver is one of the major target
organs of DV and hepatocellular
damage can occur.
Hepatic dysfunction is in dengue-
infected individuals, including painful
hepatomegaly and increased levels of
the hepatic enzymes, AST and ALT.
The elevation of liver enzymes,
predominantly AST is significantly
greater in DHF and DSS than DF.
The increase in transaminase reaching
maximum values around the 9th day
after onset of fever.
Dengue fever is characterized by :
Fever
Myalgia
Rash
Leucopenia
Thrombocytopenia
Suspected dengue cases were defined
as
Patients with reported or documented
fever of > 38 C of less than7 days duration.
Two or more symptoms or signs (headache,
rash, eye pain, myalgia, arthralgia, hypo-
tension, hemorrhage, hemoconcentration
(elevated hematocrit >20% for age and
gender, thrombocytopenia < 150.000/uL
Clinical Feature
Clinical features are often described
according to three phases :
Febrile phase
Critical phase
Convalescent phase
Dengue Fever
Dengue fever is characterized by
sudden onset of high grade fever with
non specific symptoms such as
headache, malaise, anorexia, nausea,
vomitting, weakness, rash and body
aches, flushing of the face.
DHF
DHF is caused by increased vascular
permeability cause severe plasma leakage and
may progress to hypovolemic shock, marked
thrombocytopenia, and a bleeding diathesis.
Mortality rate for untreated patients varying
between 10% and 20% but can reach as high as
40% with involvement of shock.
cont..
DHF is characterized by the presence of
:
Hemorrhagia
Thrombocytopenia < 100.000/uL
Clinical evidence of plasma leak
resulting from increased vascular
permeability.
Manifestasi Hemoragik
Capillary fragility
Petechiae, ecchymoses or purpura
Bleeding from mucosa, gastrointestinal
tract or other sites
Haematemesis or melena
Severe clinical disease manifestations such as
:
Fluid leakage
Bleeding
Shock
Are seen during the critical phase which
begins around day 4-7 of the illness and
usually lasts 48-72 hours.
DENGUE SHOCK SYNDROME
Disertai kegagalan sirkulasi, nadi
cepat dan lemah
Tekanan darah turun
Kulit dingin, lembab
Pasien gelisah
WHO criteria
DHF grade I is manifested by fever
accompanied by nonspecific
constitutional symptoms, with a
positive tourniquet test result.
DHF grade II is the appearance of
spontaneous bleeding in addition to
constitutional symptoms.
cont..
DHF grade III is circulatory failure with signs
of rapid and weak pulse, narrowing of pulse
pressure or hypotension, and the presence of
cold clammy skin.
DHF grade IV is profound shock with
undetectable blood pressure and pulse.
Grade III and IV are grouped as DSS
The 1997 WHO classification
Acute febrile illness as dengue
fever based on headache, retro-
orbital pain, myalgia, arthralgia,
rash, hemorrhagic manifestations,
and leukopenia.
The 2009 WHO classification
Uses two or more clinical manifestations for
probable dengue classification :
Nausea/vomiting, rash, aches and pains,
tourniquet test positive, leucopenia and any
warning signs.
For this analysis, leukopenia was defined as
below 4500/uL, and arthralgia/myalgia was
include under aches and pains.
To have rapid and sensitive
laboratory assay for early
detection of the disease.
There are two main methods for
diagnosing dengue infection :
Virus detection includes viral isolation,
PCR, detection of NS1 antigen.
Antibody detection includes
haemagglutination inhibition (HAI) tests
and ELISA for detection of dengue IgM and
IgG antibodies.
The major of diagnostic methods
currently available are :
Viral culture by cell culture (in C6/36 mosquito cell
line) and subsequent detection by
immunofluorescence, though the gold standard. It
is costly and time consuming as more than 7 days.
Viral RNA detection by RT-PCR, the requirement of
a highly trained staff, need of a sophisticated
equipment as well as cost factor.
Serological tests such as IgM-ELISA, has low
sensitivity in the first four days of illness.
NS1 (non structural protein 1) is a highly
conserved glycoprotein that is essential for
the viability of DV and is produced both
membrane-associated and secretory forms
by the virus.
The NS1 is a present at high concen-
tration in sera of dengue infected
patients during the early phase of
disease, and is found from day 1 and up
to day 9 after onset of fever in sample of
primary or secondary dengue-infected
patients.
The IgM become detectable on day 3 to 5 of
illness in case of primary dengue infection
and persist for 2 to 3 months, whereas IgG
appear by the fourteenth day and persist for
life.
Secondary infection shows that IgG rises
within 1 to 2 days after onset of symptoms,
simultaneously with IgM antibodies.
Laboratory-positive dengue cases are
confirmed by ELISA of specific dengue
IgM, fourfold increase of dengue-
specific IgG titers in convalescent
serum.
Laboratory Finding
Positive tourniquet test was define if there
are more than 20 petechiae in a define 2,5 cm
area.
Leucopenia < 4000/ cmm
Thrombocytopenia < 150.000/cmm
Prolong aPTT > 38 sec
Elevated serum AST or ALT > 39 U/L
Low C-reactive protein < 20 mg/L
Diagnosis Banding
Demam tifoid
Campak
Influenzae
Leptospirosis
Chikungunya
Currently, there are :
No commercially available vaccines
for prevention of dengue.
No antiviral drugs for dengue but
severe dengue may be successfully
treated with aggressive intravenous
rehydration.
Pemberian komponen darah
Trombosit : bila ada perdarahan nyata
dan berat, diberikan sampai
perdarahan berhenti
Kriopresipitat : bila fibrinogen di
bawah 100 mg/dl