Infection with one dengue serotype confers lifelong homotypic immunity to that serotype and a very brief period of partial heterotypic immunity to other serotypes, but a person can eventually be infected by all 4 serotypes. Several serotypes can be in circulation during an epidemic.
The global prevalence of dengue has grown dramatically in recent decades. The disease is now endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, South-east Asia and the Western Pacific.
Without proper treatment, DHF case fatality rates can exceed 20%. With modern intensive supportive therapy, such rates can be reduced to less than 1%. The spread of dengue is attributed to expanding geographic distribution of the four dengue viruses and of their mosquito vectors, the most important of which is the predominantly urban species Aedes aegypti.
The vectors for transmission of the dengue virus are aedes egypti and aedes albopticus.
As the term implies, dengue shock syndrome is essentially dengue hemorrhagic fever with progression into circulatory failure, with ensuing hypotension, narrow pulse pressure (< 20 mm Hg), and, ultimately, shock and death if left untreated. Death may occur 8-24 hours after onset of signs of circulatory failure. The most common clinical findings in impending shock include hypothermia, abdominal pain, vomiting, and restlessness.
Liver damage manifests as increases in levels of alanine aminotransferase and aspartate aminotransferase, low albumin levels, and deranged coagulation parameters (prothrombin time, partial thromboplastin time).[24, 25] In persons with fatal dengue hepatitis, infection was demonstrated in more than 90% of hepatocytes and Kupffer cells with minimal cytokine response (tumor necrosis factor [TNF]–alpha, interleukin [IL]–2). This is similar to that seen with fatal yellow fever and Ebola infections.
A second rash may occur within 1-2 days of defervescence, lasting 1-5 days; it is morbilliform, is maculopapular, spares the palms and soles, and occasionally desquamates. The convalescent phase may last for 2 weeks.
Single-dose methylprednisolone showed no mortality benefit in the treatment of dengue shock syndrome in a prospective, randomized, double-blind, placebo-controlled trial.
Patients may need a central intravenous line for volume replacement and an arterial line for accurate blood pressure monitoring and frequent blood tests. Exercise caution when placing intravascular catheters because of the increased bleeding complications of dengue hemorrhagic fever. Urethral catheterization may be useful to strictly monitor urine output.
At this time, patients reabsorb extravasated fluid and are at risk for volume overload if intravenous fluids are continued. Do not interpret a falling hematocrit value in a clinically improving patient as a sign of internal bleeding.
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
Dengue is transmitted by mosquitoes of the genus
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
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.
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 .
In India first outbreak of dengue was recorded in
A double peak hemorrhagic fever epidemic occurred
in India for the first time in Calcutta between July
1963 & March 1964
In New Delhi, outbreaks of dengue fever reported in5
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
Increased worldwide distribution of disease seen
after World War II
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 type-
specific virus is yellow fever.
Transmission of dengue virus into the host is through
AEDES EGYPTI AEDES ALBOPTICUS
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 reaches9
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
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
The transmission cycle of dengue virus by the
mosquito Aedes aegypti begins with a dengue-
infected person. This person will have virus
circulating in the blood—a viremia that lasts for
about five days.
During the viremic period, an uninfected female
Aedes aegypti mosquito bites the person and
ingests blood that contains dengue virus.
Then, within the mosquito, the virus replicates
during an extrinsic incubation period of eight to
The mosquito then bites a susceptible person and
transmits the virus .
The virus then replicates in the second person
and produces symptoms. The symptoms begin to
appear an average of four to seven days after the
mosquito bite—this is the intrinsic incubation
period, within humans.
It can range from 3 to 14 days (average 4-7 days).
While viral replication takes place in target
dendritic cells. Infection of target cells, primarily
those of the reticuloendothelial system, such as
dendritic cells, hepatocytes, and endothelial cells
This result in the production of immune mediators
that serve to shape the quantity, type, and duration
of cellular and humoral immune response to both
the initial and subsequent virus infections.
Fever typically begins on the third day of illness
and persists 5-7 days, abating with the cessation
of viremia. Fever may reach 41C°.
Occasionally, and more frequently in children, the
fever abates for a day and recurs, a pattern that is
termed a saddleback fever; however, this pattern is
more commonly seen in dengue hemorrhagic
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
Dengue classification :
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 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)
• Hemorrhagic manifestations(eg, petechiae,
bleeding gums, epistaxis, menorrhagia, hematuria)
Additional findings may include the following:
Facial flushing, a sensitive and specific predictor of
Inflamed pharynx, lymphadenopathy , hepatic injury
Nausea and vomiting, nonproductive cough , sore
Tachycardia, bradycardia, and conduction
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.
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.
Patients also may have symptoms related to
Based on clinical signs , travel history , ruling out
other diseases (such as malaria, typhoid fever,
rubella, measles, acute febrile syndrome)
Direct – detection of viral components :
• RT- PCR
• NS-1 AG detection by ELISA or lateral flow rapid
Indirect by serology
WHO: Guidelines for diagnosis, treatment, prevention and control Geneva 2009
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
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
DENV-1 TO 4 RT-PCR :
Useful for first five days of symptoms
80-90% sens, >90% specificity
Better sensitivity when combined with serology
FDA approved in 2012 for diagnostic use in USA
Kits were available for distribution july, 2012.IgM capture ELISA (MAC ELISA) :
Detected as early as 4 days after the onset of fever
False positive sec to cross reactivity within other
faviviridae (recent vaccines)
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
Can be done only at research labPRNT :
Plaque reduction and neutralisation assay, it’s a
most specific serology tool .
Measures titer and neutralising antibodies
Labor intensive, requires maintenance of very
specific cell lines
Limited to research lab.
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.
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.
Reduce mortality rate
Decrease the progression of disease state
Maintain hydration , platelet levels , hematocrit
Decrease the viral load in the body
To reduce the complications associated with
dengue (cardiomyopathy , hepatic injury, seizures,
Factors that affect disease severity and prognosis
include the following:
Sequence of infection with different dengue
Quality and extent of available medical care
NON PHARMACOLOGICAL :
Vector Control Methods:
1.Biological and Environmental 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
. Larvicides may be used to kill immature aquatic
. Ultra-low volume fumigation against adult
Supportive only as there is no antiviral against
Oral rehydration therapy is recommended for
patients with moderate dehydration caused by high
fever and vomiting. Antipyretic (acetaminophen
325-600mg Q4hr) to be given to reduce fever .
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
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
– 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
Admission for intravenous fluid administration is
indicated for patients who develop signs of
dehydration, such as the following:
Prolonged capillary refill time
Cool or mottled skin
Diminished pulse amplitude
Altered mental status
Decreased urine output
Rising hematocrit (polycythemia)
Narrowed pulse pressure
In DHF , blood transfusion is required (if significant
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.
Patients with internal or gastrointestinal bleeding may
require transfusion, and patients with coagulopathy
may require fresh frozen plasma.
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
Special population :
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.
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
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
The use of mosquito netting is of limited benefit, as
Aedes are day-biting mosquitoes
Eliminate the mosquito vector using indoor sprays
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
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
Wagner D, de With K, Huzly D, Hufert F, Weidmann M,
Breisinger S, et al. Nosocomial acquisition of dengue.
Emerg Infect Dis. 2004 Oct. 10(10):1872-3
"Travelers' Health Outbreak Notice". Centers for
Disease Control and Prevention. 2 June 2010.
Center for Disease Control and Prevention. "Chapter 5
dengue fever (DF) and dengue hemorrhagic fever
WHO : Guidelines for diagnosis, treatment, prevention
ACTION AGAINST DENGUE Dengue Day
Campaigns Across Asia. World Health