DENGUE FEVER

Dr.T.V.Rao MD
Professor of Microbiology
 Arboviruses

The Arboviruses are also called as

Arthropod borne viruses, represent an
ecological grounding of viruses with
complex transmission cycles involving
Arthropods
These viruses have diverse physical and
chemical properties and are classified in
several virus families.
Dengue infection is caused by Arboviruses
 History Dengue
This disease was first described 1780, and
the virus was isolated by Sabin 1944.
Dengue virus infection is the most
common arthropod-borne disease
worldwide with an increasing incidence in
the tropical regions of Asia, Africa, and
Central and South America. There are four
serotypes of the virus. All are transmitted
by mosquitoes, which are not affected by
the disease, although an infected
mosquito may infect others (not via man).
 Current Trends
In the 1980s, DHF began a second
expansion into Asia when Sri Lanka, India,
and the Maldives Islands had their first
major DHF epidemics; Pakistan first
reported an epidemic of dengue fever in
1994. The epidemics in Sri Lanka and
India were associated with multiple
dengue virus serotypes, but DEN-3 was
predominant and was genetically distinct
from DEN-3 viruses previously isolated
from infected persons in those countries.
Prevalence of Dengue Infection
 Dengue Infection and
Implications
Dengue virus (DENV) infects 50 million
(WHO) to 100 million (NIH) people
annually. Forty percent of the world’s
population, predominately in the tropics
and sub-tropics, is at risk for contracting
dengue virus. DENV infection can cause
dengue fever, dengue hemorrhagic fever,
dengue shock syndrome, and death.
 Dengue
Mosquito traanmitted Viral Infection
 What causes Dengue
Dengue (DF) and dengue hemorrhagic
fever (DHF) are caused by one of four
closely related, but antigenically distinct,
virus serotypes (DEN-1, DEN-2, DEN-3,
and DEN-4), of the genus Flavivirus.
Infection with one of these serotypes
provides immunity to only that serotype for
life,
 Aedes aegypti – Vector

Aedes aegypti, a domestic, day-biting

mosquito that prefers to feed on humans,
is the most common Aedes species.
Infections produce a spectrum of clinical
illness ranging from a nonspecific viral
syndrome to severe and fatal hemorrhagic
disease. Other species of Aedes can also
transmit.
 Dengue Virus – A Flavivirius
Flavivirius are spherical
and 40- 60 mm in
diameter.
Genome – Positive
sense, single sense
RNA,11kb in size
Genome – RNA
infectious
Enveloped virus
Three structural
polypeptides two are
glycosylated
Replication in cytoplasam
How Mosquitos spread the infection

The disease starts during the rainy season,

when vector Mosquito Aedes aegypti is
abundant
The Aedes breeds in the tropical or semitropical
climates in water holding receptacles or in plants
close to human dwellings
A female Aedes acquires the infection feeding
upon a viremic human.
After a period of 8 – 14 days mosquitoes are
infective and remain infective for life. ( 1- 3 )
months.
 Dengue - Endemics
Persons living in a dengue-endemic area
can have more than one dengue infection
during their lifetime. DF and DHF are
primarily diseases of tropical and sub
tropical areas, and the four different
dengue serotypes are maintained in a
cycle that involves humans and the Aedes
mosquito.
 Clinical Manifestations
Any or few of the following events can
occur.
Fever,
Severe head ache
Muscle and joint pains
Nausea, vomiting,
Eye pain
How Dengue Infection starts and
manifests
Incubation period 4 – 7 days ( 3 – 14 days)
Fever may start with, Malise,chills,head ache
Soon leads to severe back ache, joint pains, muscular
pain, pain in the eye ball.
Temperature may persist for 3 -5 days.
On some occasions once again raises in about 5 – 8
days ( Saddle back fever )
Myalgia may be severe with deep bone pain
( Break bone fever ) characteristic of the Disease
On majority of the occasions a self limited
condition,
Subside on its own
Death is a rare event.
Dengue with Rashes
 Dengue Hemorrhagic Fever
Common in children.
In children passively acquired contributed
by the maternal antibodies transferred to
the fetus.
In other ( Adults ) the presence of
antibodies due to previous infection with
different serotype
Initially presents like classical Dengue
infection
But patients condition abruptly worsens,
an important cause of morbidity and
 Risk factor for DHF
Important risk factors for DHF include the
strain of the infecting virus, as well as the
age, and especially the prior dengue
infection history of the patient
Dengue Hemorrhagic Syndrome
Chateresied by shock and
hemoconcentration
Contributed by circustantial evidence
suggests secondary infection with Dengue
type 2 following type 1 infection in the
past.
 Pathogenesis

Presence of existing Dengue antibody,

associated with fresh viral infection with
new serotype complexes and forms within
few days of the second dengue infection.
Non neutralizing enhancing antibodies
promote infection of higher number of
Mononuclear cells.
 Dengue Hemorraghigic
Syndrome
DHS is caused due to release of,
1 Release of cytokines
2 Vasoactive mediators.
3 Procoagulants
Manifest with disseminated
intravascular coagulation
 Risk of Hemorrhagic Fever
The risk of hemorrhagic fever syndrome is about
0.2% during the first attack
The second attack with different serotype
increases the risk to ten fold
The fatality rate with dengue hemorrhagic fever
can reach 15% but proper medical care and
symptomatic mangement can reduce mortality to
less than 1%
On few occasions patients condition abruptly
worsens into Dengue shock syndrome, a more
severe form of disease characterized by shock
and hemoconcentration.
 Diagnosis
In resource rich establishments
1 Reverse transcriptase polymerase chain
reaction methods help rapid identification
2 Isolation of virus is difficult
3 The current favored approach is
inoculation of mosquito cell line with
patient serum coupled with nucleic acid
assay to identify a recovered virus.
 Dengue Serology
The serology is limited with cross reactivity of
IgG antibodies to heterologus Flavivirius
antigens
Most commonly used methods are
Viral protein specific capture IgM or IgG by
ELISA
IgM antibodies develop within few days of
illness
Neutralizing anti Hemagglutination inhibiting
antibodies appear within a week after onset of
Dengue fever
 Importance of paired sample
testing in Serology

Testing one sample for serum and

reporting a negative test is fallacious
Analysis of paired acute and
convalescent sera to show
significant rise in antibody titer is
the most reliable evidence of an
active dengue infection.
 Newer Diagnostic Methods
RT - PCR

RT PCR is a highly
sensitive tool in
Diagnosis, with
established high
sensitivity in
Diagnosis in Puzzles
Developing world
lacks resources to
implement and utilize
the Scientific
advances
 Immunology in Dengue

Four serotypes exist distinguished by

Molecular basis and Nt tests
Infection confers life long immunity
But cross protection between serotypes is
of short duration.
Reinfection with different serotype after
primary attack is more dangerous causes
Dengue hemorrhagic fever.
 Treatment
No Anti viral therapy available
Symptomatic management in Majority of
cases
Dengue Hemorrhagic fever to be treated
with suitable fluid replacement
No Vaccine available, difficult in view of
four serotypes.
 Control of Dengue
Control of Mosquito breeding places.
Anti mosquito measures
Use of Insecticides.
Screened windows and doors can reduce
exposure to vectors.
 Epidemiology - Dengue
Dengue virus are distributed world wide in
tropical regions.
Where the Aedes vectors exist, are
endemic areas
Changing and increasing incidences are
associated with rapid urban population
growth, over crowding and lax mosquito
control measures
Dengue a Reemerging Infection

Dengue in 2005 identified as the most

important mosquito borne viral disease
An estimated 50 million or more cases
occur annually worldwide
400,000 cases of dengue hemorrhagic
fever.
Asian counties report major cases of
childhood deaths
Avoiding Mosquito bites remain
only way to prevent Dengue
Created for Benefit of Medical Health care
workers in Developing World

Dr.T.V.Rao MD
Email
doctortvrao@gmail.com