DENGUE FEVER

Dr.T.V.Rao MD

Dr.T.V.Rao MD 1
 Arboviruses
• The Arbovirus 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
Arbovirus Dr.T.V.Rao MD 2
Man-Arthropod-Man Cycle
 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).
Dr.T.V.Rao MD 4
 Over view of Dengue
• With more than one-third of the world’s
population living in areas at risk for
transmission, dengue infection is a
leading cause of illness and death in the
tropics and subtropics. As many as 100
million people are infected yearly.
Dengue is caused by any one of four
related viruses transmitted by
mosquitoes Dr.T.V.Rao MD 5
 Dengue
• Dengue is the biggest Arbovirus problem in the world today with
over 2 million cases per year. Dengue is found in SE Asia, Africa and
the Caribbean and S America.
• Flavivirus, 4 serotypes, transmitted by Aedes mosquitoes which reside
in water-filled containers.
• Human infections arise from a human-mosquitoe-human cycle
• Classically, dengue presents with a high fever, lymphadenopathy,
myalgia, bone and joint pains, headache, and a Maculopapular rash.
• Severe cases may present with hemorrhagic fever and shock with a
mortality of 5-10%. (Dengue hemorrhagic fever or Dengue shock
syndrome.)
 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.
Dr.T.V.Rao MD 7
Distribution of Dengue
Dr.T.V.Rao MD 9
 Dengue Infection and
Implications
• Dengue virus (DENV) infects 50 million
(WHO) to 100 million (NIH) people
annually. Forty per cent 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
haemorrhagic fever, dengue shock
syndrome, and death.
Dr.T.V.Rao MD 10
 Dengue
Mosquito transmitted Viral Infection

Dr.T.V.Rao MD 11
 What causes Dengue
• Dengue (DF) and dengue haemorrhagic
fever (DHF) are caused by one of four
closely related, but antigenic ally 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,
Dr.T.V.Rao MD 12
 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 haemorrhagic
disease. Other species of
Aedes can also transmit.

Dr.T.V.Rao MD 13
 Dengue Virus – A Flavivirus
• Flavivirus 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 cytoplasm

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 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.

Dr.T.V.Rao MD 15
 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.

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 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.

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 Immunology 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.
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 Clinical Manifestations
• Any or few of the following events can
occur.
• Fever,
• Severe head ache
• Muscle and joint pains
• Nausea, vomiting,
• Eye pain
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Dr.T.V.Rao MD 20
 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.
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Dengue with Rashes

Dr.T.V.Rao MD 22
 Dengue Hemorrhagic Fever
• DHF was first recognized in the 1950s during the
dengue epidemics in the Philippines and
Thailand. By 1970 nine countries had experienced
epidemic DHF and now, the number has
increased more than fourfold and continues to
rise. Today emerging DHF cases are causing
increased dengue epidemics in the Americas, and
in Asia, where all four dengue viruses are
endemic, DHF has become a leading cause of
hospitalization and death among children in
several countries. ( WHO )

Dr.T.V.Rao MD 23
 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 mortality in
Dengue

Dr.T.V.Rao MD 24
Symptoms of Dengue Hemorrhagic Fever

• The severe form of dengue typically starts like the

mild form but gets a lot worse after a couple of
days. Along with the symptoms above, dengue
hemorrhagic fever may also cause:
• – Drastically reduced blood cells, making blood
clotting difficult
– Significantly damaged lymph and blood vessels
– Mouth and nose bleeding
– Bleeding underneath the skin that typically
looks like bruises
– Death

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 Basic Understanding of Dengue
Hemorrhagic Fever
• Dengue Hemorrhagic Fever is a probable case of
dengue and
• hemorrhagic tendency evidenced by one or more
of the following:
• Ø Positive tourniquet test
• Ø Petechial, ecchymosis or purpura
• Ø Bleeding from mucosa (mostly epistaxis or
bleeding from
• gums), injection sites or other sites
• Ø Haematemesis or melena

Dr.T.V.Rao MD 26
 How to do a Tourniquet test
• The tourniquet test is performed
by inflating a blood pressure cuff
to a point mid-way between the
systolic and diastolic pressures for
five minutes. A test is considered
positive when 10 or more
petechiae per 2.5 cm2 (1 inch)
are observed. In DHF, the test
usually gives a definite positive
result (i.e. >20 petechiae). The
test may be negative or mildly
positive during the phase of
profound shock.

Dr.T.V.Rao MD 27
 What Happens in Dengue
Hemorrhagic Fever
• Thrombocytopenia (platelets 100,000/cu.mm or less)
and Ø Evidence of plasma leakage due to increased
capillary permeability manifested by one or more of
the following:
• – A >20% rise in hematocrit for age and sex
• – A >20% drop in hematocrit following treatment
with
• fluids as compared to baseline
• – Signs of plasma leakage (pleural effusion, ascites or
• hypoproteinaemia).
Dr.T.V.Rao MD 28
 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

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 Dengue Hemorrhagic Syndrome
• Chateresied by shock
and
hemoconcentration
• Contributed by
circumstantial
evidence suggests
secondary infection
with Dengue type 2
following type 1
infection in the past.
Dr.T.V.Rao MD 30
 Dengue hemorraghigic Syndrome
• DHS is caused due to release of,
1 Release of cytokines
2 Vasoactive mediators.
3 Procoagulants
Manifest with disseminated
intravascular coagulation

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 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
management 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.
Dr.T.V.Rao MD 32
 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.
Dr.T.V.Rao MD 33
 Dengue Serology
• The serology is limited with cross reactivity of
IgG antibodies to heterologous Flavivirus
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 Haemagglutination inhibiting antibodies
appear within a week after onset of Dengue fever
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 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.
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 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

Dr.T.V.Rao MD 36
 Caring Dengue patients (WHO)
• All dengue patients must be carefully observed for
complications for at least 2 days after recovery from
fever. This is because life threatening complications
often occur during this phase. Patients and households
should be informed that severe abdominal pain,
passage of black stools, bleeding into the skin or from
the nose or gums, sweating, and cold skin are danger
signs.
• If any of these signs is noticed, the patient should be
taken to the hospital.. The patient who does not have
any evidence of complications and who has been
afebrile for 2-3 days does not need further
observation.
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 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.

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 Control of Dengue
• Control of Mosquito breeding
places.
• Anti mosquito measures
• Use of Insecticides.
• Screened windows and doors can
reduce exposure to vectors.
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 WHO guidelines for Control of
Dengue
• Activities to control transmission should target Ae. aegypti
(the main vector) in the habitats of its immature and adult
stages in the household and immediate vicinity, as well as
other settings where human–vector contact occurs (e.g.
schools, hospitals and workplaces), unless there is sound
evidence that Ae. albopictus or other mosquito species are
the local vectors of dengue. Ae. aegypti proliferates in many
purposely-filled household containers such as those used for
domestic water storage and for decorative plants, as well as in
a multiplicity of rain-filled habitats – including used tyres,
discarded food and beverage containers, blocked gutters and
buildings under construction. Typically, these mosquitoes do
not fly far, the majority remaining within 100 metres of where
they emerged. They feed almost entirely on humans, mainly
Dr.T.V.Rao MD 40
during daylight hours, and both indoors and outdoors
 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
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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

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