DENGUE FEVER

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 CONTENTS :
 Introduction
 Etiology
 Classification
 Clinical presentation
 Diagnosis
 Management
 Prevention
 Vaccines

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 INTRODUCTION
 Dengue fever is an acute infectious viral disease,
also known as breakbone fever.
 It is a arthropod-borne (arboviral ) illness in human .
It is caused by infection with 1 of the 4 serotypes of
dengue virus (DENV1,2,3,4), which is a Flavivirus
(a genus of single-stranded nonsegmented RNA
viruses).
 Once affected persons acquire long-life serotype
specific immunity.
 Dengue is transmitted by mosquitoes of the genus
Aedes and species aegypti and albopticus.
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 Dr Benjamin Rush a professor of chemistry and
medical theory at the UPEN, during the
Philadelphia epidemic 1779 -1780 , first described
the dramatic symptoms of dengue as break bone
fever.
 A small percentage of persons who have previously
been infected by one dengue serotype develop
bleeding and endothelial leak up on infection with
another dengue serotype. This syndrome is termed
dengue hemorrhagic fever (DHF). Also been
termed dengue vasculopathy.

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 Vascular leakage in these patients results in
hemoconcentration and serious effusions and can
lead to circulatory collapse.
 This, in conjunction with severe hemorrhagic
complications, can lead to dengue shock
syndrome(DSS), which poses a greater fatality risk
than bleeding .

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


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 An estimated 5,00,000 cases of DHF require
hospitalization each year, of which a very large
proportion are children. At least 2.5% of cases die
without proper treatment.
 A rapid rise in urban populations is bringing greater
numbers of people into contact with this vector,
especially in areas that are favorable for mosquito
breeding, e.g. where household water storage is
common and where solid waste disposal services
are inadequate.
 Increased worldwide distribution of disease seen
after World War II

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Etiology :
 Dengue infection is caused by dengue virus
(DENV), which is a single-stranded RNA virus
(approximately 11 kilobases long) with an
icosahedral nucleocapsid and covered by a lipid
envelope. The virus is in the family Flaviviridae,
genus Flavivirus, and the typespecific virus is
yellow fever.
 Transmission of dengue virus into the host is
through

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the vectors
AEDES EGYPTI AEDES ALBOPTICUS

http://www.cdc.gov/dengue/vector

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 Dengue is transmitted by infected female mosquito.
 A.egypti is a primarily a daytime feeder. It lives
around human habitation.
 Lays eggs and produces larvae preferentially in
artificial containers . Only the female aedes
mosquito bites as it needs the protein in blood to
develop its eggs.
 The mosquito becomes infective approximately 7
days after it has bitten a person carrying the virus.
 This is the extrinsic incubation period, during which
time the virus replicates in the mosquito and
reaches the salivary glands.

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 The mosquito remains infected for the remainder of
its life. The life span of A aegypti is usually 21 days
but ranges from 15 to 65 days.
 The mosquito can lay eggs about 3 times in its
lifetime, and about 100 eggs are produced each
time.
 The eggs can lie dormant in dry conditions for up to
about 9 months, after which they can hatch if
exposed to favourable conditions, i.e. water and
food.

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Dengue classification:
There are actually four dengue clinical syndromes:
• Undifferentiated fever;
• Classic dengue fever;
• Dengue hemorrhagic fever, or DHF; and
• Dengue shock syndrome, or DSS.
• Dengue shock syndrome is actually a severe form
of DHF.

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Clinical presentation :
 Prodrome of chills, erythematous mottling of the
skin, and facial flushing (a sensitive and specific
indicator of dengue fever). The prodrome may last
for 2-3 days.
 Children younger than 15 years usually have a
nonspecific febrile syndrome, which may be
accompanied by a maculopapular rash.
 Classic dengue fever begins with sudden onset of
fever, chills, and severe (termed breakbone) aching
of the head, back, and extremities, as well as other
symptoms. The fever lasts 2-7 days and may reach
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 41°C. Fever that lasts longer than 10 According to
the Pan American Health Organization (PAHO), the
clinical description of dengue fever is an acute
febrile illness of 2-7 days duration associated with 2
or more of the following:
• Severe and generalized headache
• Retro-orbital pain
• Severe myalgia's, especially of the lower back,
arms, and legs
• Arthralgia's, usually of the knees and shoulders
• Characteristic rash (maculopapular)

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• Hemorrhagic manifestations(eg, petechiae, bleeding
gums, epistaxis, menorrhagia, hematuria) •
Thrombocytopenia • Leukopenia.
Additional findings may include the following:
 Injected conjunctivae
 Facial flushing, a sensitive and specific predictor of
dengue infection
 Inflamed pharynx, lymphadenopathy , hepatic injury
 Nausea and vomiting, nonproductive cough , sore
throat
 Tachycardia, bradycardia, and conduction
defects,anorexia

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 Increasing hematocrit (20% absolute rise from
baseline) and low albumin (signs of
hemoconcentration preceding shock), more obvious
hemorrhagic manifestations (>50% of patients have
a positive tourniquet test), and progressive effusions
(pleural or peritoneal)
 Fever typically abates with the cessation of viremia.
Occasionally, and more commonly in children, the
fever abates for a day and then returns, a pattern
that has been called saddleback fever.
 Patients are at risk for development of dengue
hemorrhagic fever or dengue shock syndrome at
approximately the time of defervescence.
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 Abdominal pain in conjunction with restlessness,
change in mental status, hypothermia, and a drop in
the platelet count presages the development of
dengue hemorrhagic fever.
 If left untreated, dengue hemorrhagic fever most
likely progresses to dengue shock syndrome.
Common symptoms in impending shock include
abdominal pain, vomiting, and restlessness.

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Patients also may have symptoms related to
circulatory failure.

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WHO: Guidelines for diagnosis, treatment, prevention and control Geneva 2009

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Diagnosis :
 Based on clinical signs , travel history , ruling out
other diseases (such as malaria, typhoid fever,
rubella, measles, acute febrile syndrome)
Diagnostic tests
Direct – detection of viral components :
• RT- PCR
• NS-1 AG detection by ELISA or lateral flow rapid
test
Indirect by serology

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WHO: Guidelines for diagnosis, treatment, prevention and control Geneva 2009

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NS- 1 Ag :
 Structural protein secreted by all flaviviridae
 Detectable upto 10 days after onset of illness
 Disappear once seroconversion has occurred
 ELISA/rapid test lat flow serology NS-1 specific IgM,
IgG
 Many commercial rapid test :15mn
 Not FDA approved
 Sensitivity in first 5 days – febrile phase, >90% for
primary infection, 60-80 % for secondary infection.
 Cross reactivity due to other flaviviridae.
 Lateral flow test : IgG, IgM, NS-1 Ag ( not available
in US)
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DENV-1 TO 4 RT-PCR :
 Useful for first five days of symptoms
 80-90 % sens, >90% specificity
 Better sensitivity when combined with serology
follow
 FDA approved in 2012 for diagnostic use in USA
IgM capture ELISA (MAC ELISA) :Kits were
available for distribution july, 2012.
 Detected as early as 4 days after the onset of fever
 False positive sec to cross reactivity within other
faviviridae (recent vaccines)
 Sensitivity 61.5-99 %
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 FDA approved MAC -ELISA in april 2011
 If negative even then repeated within 6 days—>
PCR or NS-1 Ag
Viral cell culture :
 Its confirmatory , identifies serotype .
 Needs acute serum sample(first 5 days)
 Does not differentiate between primary and
secondary
PRNT :Can be done only at research lab
 Plaque reduction and neutralisation assay, it’s a
most specific serology tool .
 Measures titer and neutralising antibodies
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 Labor intensive, requires maintenance of very
specific cell lines
 Limited to research lab.
Management :
General approach :
 Dengue fever is usually a self-limited illness.
 There is no specific antiviral treatment currently
available for dengue fever.
 Supportive care with analgesics, fluid replacement,
and bed rest is usually sufficient.
 Aspirin, nonsteroidal anti-inflammatory drugs
(NSAIDs), and corticosteroids should be avoided.
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 Management of severe dengue requires careful
attention to fluid management and proactive
treatment of hemorrhage.
 The Novartis Institute for Tropical Diseases (NITD)
in Singapore is carrying out research to find
inhibitors of dengue viral target proteins to reduce
the viral load during active infection.
GOALS :
 Reduce mortality rate
 Decrease the progression of disease state
 Maintain hydration , platelet levels , hematocrit levels
 Decrease the viral load in the body

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 To reduce the complications associated with dengue
(cardiomyopathy , hepatic injury, seizures,
pneumonia etc.)
Factors that affect disease severity and prognosis
include the following:
 Patient age Pregnancy
 Nutritional status
 Ethnicity
 Sequence of infection with different dengue
serotypes
 Virus genotype
 Quality and extent of available medical care

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NON PHARMACOLOGICAL :
MOSQUITO
BED REPELLEN
REST TS
FOR
DHF/DSS

FLUID
INTAKE
VECTOR
CONTRO MAINTAIN
L HYGEINE
METHOD
S

PATIENT
EDUCATION

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Vector Control Methods:
1.Biological and Environmental Control
2.Biological control
. Largely experimental
. Option: place fish in containers to eat larvae
. Environmental control
Elimination of larval habitats
. Most likely method to be effective in the long term
3.Chemical Control:
. Larvicides may be used to kill immature aquatic
stages
 . Ultra-low volume fumigation against adult
mosquitoes
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. Mosquitoes may have resistance to commercial
PHARMACOLOGICAL :
 Supportive only as there is no antiviral against
DENV
 Oral rehydration therapy is recommended for
patients with moderate dehydration caused by high
fever and vomiting. Antipyretic (acetaminophen 325-
600 mg Q4hr) to be given to reduce fever .

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 Patients with known or suspected dengue fever
should have their platelet count and hematocrit
measured daily from the third day of illness until 1-2
days after defervescence.
 Patients who develop signs of dengue hemorrhagic
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fever warrant closer observation(ICU).

Activities at the first level of care should focus on:
– recognizing that the febrile patient could have
dengue;
– notifying early to the public health authorities that the
patient is a suspected case of dengue;
 – managing patients in the early febrile phase of
dengue;
– recognizing the early stage of plasma leakage or
critical phase and initiating fluid therapy;
– recognizing patients with warning signs who need to
be referred for admission and/or intravenous fluid
therapy to a secondary health care facility;
– recognizing and managing severe plasma leakage
and shock, severe bleeding and severe organ

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Admission for intravenous fluid administration is
indicated for patients who develop signs of dehydration,
such as the following:
 Tachycardia
 Prolonged capillary refill time
 Cool or mottled skin
 Diminished pulse amplitude
 Altered mental status
 Decreased urine output
 Rising hematocrit (polycythemia)
 Narrowed pulse pressure
 Hypotension

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 In DHF , blood transfusion is required (if significant
bleeding)
 Intravascular volume deficits should be corrected
with isotonic fluids such as Ringer lactate solution.
Boluses of 10-20 mL/kg should be given over 20
minutes and may be repeated.
 If this fails to correct the deficit, the hematocrit value
should be determined. If it is rising, limited clinical
information suggests that a plasma expander may be
administered. Starch, dextran 40, or albumin 5% at a
dose of 10-20 mL/kg may be used.

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 Patients with internal or gastrointestinal bleeding may
require transfusion, and patients with coagulopathy
may require fresh frozen plasma.

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 After patients with dehydration are stabilized, they
usually require intravenous fluids for no more than
24-48 hours. Intravenous fluids should be stopped
when the hematocrit falls below 40% and adequate
intravascular volume is present.
Patients with dengue hemorrhagic fever or dengue
shock syndrome may be discharged from the hospital
when they meet the following criteria: Afebrile for
24 hours without antipyretics
 Good appetite, clinically improved condition
 Adequate urine output, stable hematocrit level
 At least 48 hours since recovery from shock
 No respiratory distress, platelet count greater than
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 50,000 cells/μL

Special population :
Pregnancy :
 Dengue in pregnancy must be carefully differentiated
from preeclampsia.
 An overlap of signs and symptoms, including
thrombocytopenia, capillary leak, impaired liver
function, ascites, and decreased urine output may
make this clinically challenging.

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  Pregnant women with dengue fever respond well to
the usual therapy of fluids, rest, and antipyretics.
 If the mother acquires infection in the peripartum
period, newborns should be evaluated for dengue
with serial platelet counts and serological studies

Monitoring parameters :
 Body temperature
 Respiratory rate
 Heart rate
 Blood pressure
 Pulse pressure/ volume
 Capillary refill time
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 Abdominal pain
 Bleeding
 Vomiting
Prevention :
 The only way to prevent dengue virus acquisition is
to avoid being bitten by a vector mosquito.
 Wear N,N-diethyl-3-methylbenzamide (DEET)–
containing mosquito repellant
 Wear protective clothing, preferably impregnated with
permethrin insecticide
 Remain in well-screened or air-conditioned places

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 The use of mosquito netting is of limited benefit, as
Aedes are day-biting mosquitoes
 Eliminate the mosquito vector using indoor sprays
Vaccines :
 No vaccine is currently approved for the prevention of
dengue infection.
 Because immunity to a single dengue strain is the
major risk factor for dengue hemorrhagic fever and
dengue shock syndrome, a vaccine must provide
high levels of immunity to all 4 dengue strains to be
clinically useful.

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 Tetravalent LA dengue virus strains based on yellow
fever –dengue virus [CYD-TDV]
 Future directions : TV003 a single dose of LATV –
induced a trivalent or greater Nab response in 90% of
flavivirus-naive adults

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