DENGUE FEVER
INTRODUCTION
Dengue fever , also known as breakbone fever, is an
infectious tropical disease caused by the dengue virus.
Symptoms include fever, headache, muscle and
joint pains, and a characteristic skin rash that is
similar to measles. In a small proportion of cases the
disease develops into the life-threatening dengue
hemorrhagic fever, resulting in bleeding,
low levels of blood platelets and blood plasma leakage,
or into dengue shock syndrome, where
dangerously low blood pressure occurs
Dengue is transmitted by several species of mosquito
within the genus Aedes, principally A. aegypti. The
virus has four different SERO types; infection with one
type usually gives lifelong immunity to that type, but
only short-term immunity to the others. Subsequent
infection with a different type increases the risk of
severe complications. As there is no commercially
available vaccine, prevention is sought by reducing the
habitat and the number of mosquitoes and limiting
exposure to bites.
Treatment of acute dengue is supportive, using
either oral or intravenous rehydration for mild or
moderate disease, and intravenous fluids and
blood transfusion for more severe cases.
Apart from eliminating the mosquitoes, work is
ongoing on a vaccine, as well as medication
targeted directly at the virus.
SIGNS AND SYMPTOMS
Typically, people infected with dengue virus are
asymptomatic (80%) or only have mild symptoms such as
an uncomplicated fever. Others have more severe illness
(5%), and in a small proportion it is life-threatening.
The incubation period (time between exposure and onset of
symptoms) ranges from 3–14 days, but most often it is 4–7
days. Therefore, travelers returning from endemic areas
are unlikely to have dengue if fever or other symptoms start
more than 14 days after arriving home.
Children often experience symptoms similar to those of the
common cold and gastroenteritis (vomiting and diarrhea)
and have a greater risk of severe complications, though
initial symptoms are generally mild but include high fever.
SYMPTOMS OF
DENGUE:
The characteristic symptoms of dengue are
sudden-onset fever, headache (typically located behind
the eyes), muscle and joint pains, and a rash. The
alternative name for dengue, "breakbone fever",
comes from the associated muscle and joint pains.
The course of infection is divided into three phases:
febrile, critical, and recovery.
FEBRILE PHASE
The febrile phase involves high fever, often over 40
°C (104 °F), and is associated with generalized
pain and a headache; this usually lasts two to
seven days. Vomiting may also occur.
A rash occurs in 50–80% of those with symptoms in
the first or second day of symptoms as flushed skin, or
later in the course of illness (days 4–7), as a
measles-like rash.
Some petechiae (small red spots that do not
disappear when the skin is pressed, which are caused
by broken capillaries) can appear at this point, as may
some mild bleeding from the mucous membranes of
the mouth and nose.
CRITICAL
PHASE
In some people, the disease proceeds to a critical phase.
During this phase there may be significant fluid
accumulation in the chest and abdominal cavity due to
increased capillary permeability and leakage. This leads to
depletion of fluid from the circulation and
decreased blood supply to vital organs.
During this phase, organ dysfunction and severe bleeding,
typically from the gastrointestinal tract, may occur.
Shock (dengue shock syndrome) and hemorrhage
(dengue hemorrhagic fever) occur in less than 5% of all
cases of dengue, however those who have previously been
infected with other serotypes of dengue virus ("secondary
infection") are at an increased risk. This critical phase, while
rare, occurs relatively more commonly in children and
young adults.
RECOVERY
PHASE
The recovery phase occurs next, with resorption
of the leaked fluid into the bloodstream. This
usually lasts two to three days.
The improvement is often striking, but there may
be severe itching and a slow heart rate.
Another rash may occur with either a
maculopapular or a vasculitic appearance,
which is followed by. peeling of the skin.
During this stage, a fluid overload state may
occur; if it affects the brain, it may cause a
reduced level of consciousness or seizures. A
feeling of fatigue may last for weeks in adults.
CAUSE
VIROLOGY
Dengue fever virus (DENV) is an RNA virus of the family
Flaviviridae; genus Flavivirus. Most are transmitted by
arthropods (mosquitoes or ticks), and are therefore also
referred to as arboviruses (arthropod-borne viruses).
The dengue virus genome (genetic material) contains
about 11,000 nucleotide bases, which code for the three
different types of protein molecules (C, prM and E) that
form the virus particle and seven other types of protein
molecules (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5)
that are only found in infected host cells and are
required for replication of the virus.
There are four strains of the virus, which are called
serotypes, and these are referred to as DENV-1, DENV-2,
DENV-3 and DENV-4.
TRANSMISSION
Dengue virus is primarily transmitted by Aedes mosquitoes,
particularly A. aegypti. They typically bite during the day,
particularly in the early morning and in the evening. Humans
are the primary host of the virus, but it also circulates in
nonhuman primates. An infection can be acquired via a
single bite.
A female mosquito that takes a blood meal from a person
infected with dengue fever becomes itself infected with the
virus in the cells lining its gut.
About 8–10 days later, the virus spreads to other tissues
including the mosquito's salivary glands and is subsequently
released into its saliva.
The virus seems to have no detrimental effect on the
mosquito, which remains infected for life. Aedes
aegypti prefers to lay its eggs in artificial water
containers, to live in close proximity to humans, and to
feed on people rather than other vertebrates.
Dengue can also be transmitted via infected
blood products and through organ donation
Vertical transmission (from mother to child) during
pregnancy or at birth has been reported
1. Eggs
2. Larvae
3. Pupae
4. Adult
LIFE CYCLE OF AEDES
AEGYPTI
TRANSMISSION CYCLE - 1
Transmission from human to human requires the same
female mosquito to bite a viremic human and then bite a
susceptible human at an interval of around 10-12 days
TRANSMISSION CYCLE - 2
Cycle in the mosquito
TRANSMISSION CYCLE - 3
Viremia
Extrinsic Incubation period
Intrinsic Incubation period
Viremia
MECHANISM/
PATHOGENESIS
When a mosquito carrying dengue virus bites a person, the
virus enters the skin together with the mosquito's saliva. It
binds to and enters white blood cells, and reproduces
inside the cells while they move throughout the body. The
white blood cells respond by producing a number of
signaling proteins, such as cytokines and interferons, which
are responsible for many of the symptoms, such as the
fever, the flu-like symptoms and the severe pains.
In severe infection, the virus production inside the body is
greatly increased, and many more organs (such as the liver
and the bone marrow) can be affected, and fluid from the
bloodstream leaks through the wall of small blood vessels
into body cavities.
As a result, less blood circulates in the blood vessels,
and the blood pressure becomes so low that it
cannot supply sufficient blood to vital organs.
Furthermore, dysfunction of the bone marrow leads
to reduced numbers of platelets, which are
necessary for effective blood clotting; this increases
the risk of bleeding, the other major complication of
dengue fever.
DIAGNOSIS
WARNING SIGNS
Worsening abdominal pain
Ongoing vomiting
Liver enlargement
Mucosal bleeding
High hematocrit with low platelets
Lethargy or restlessness
Serosal effusions
The diagnosis of dengue is typically made clinically, on the
basis of reported symptoms and physical examination;
However, early disease can be difficult to differentiate from
other viral infections. A probable diagnosis is based on the
findings of fever plus two of the following: nausea and
vomiting, rash, generalized pains,
low white blood cell count, positive tourniquet test, or any
warning sign in someone who lives in an endemic area.
Dr.T.V.Rao MD
30
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.
The earliest change detectable on laboratory
investigations is a low white blood cell count, which may
then be followed by low platelets with moderately
elevated level of aminotransferase
In severe disease, plasma leakage results in
hemoconcentration (as indicated by a rising hematocrit)
and hypoalbuminemia.
Pleural effusions or ascites can be detected by physical
examination when large, but the demonstration of fluid on
ultrasound may assist in the early identification of dengue
shock syndrome.
Dengue shock syndrome occurs if pulse pressure drops to
≤ 20 mm Hg while peripheral vascular collapse is
evidenced.
FOUR CRITERIA FOR
DHF
Fever, last for 2-7days
at least one of Hemorrhage evidences
Thrombocytopenia :PLT<100,000/mm3
Evidence of plasma leakage:
• a rise in Hct: >=20%
• pleural effusion ,ascites and hypoprotinemia
LABORATORY
TESTS
Dengue fever may be diagnosed by microbiological
laboratory testing. This can be done by virus isolation in
cell cultures, nucleic acid detection by PCR, viral antigen
detection (such as for NS1 i.e. non structural protein test
detect antigen on 1st
day of attack) or specific antibodies
(serology).
All tests may be negative in the early stages of the
disease. PCR and viral antigen detection are more
accurate in the first seven days.
Tests for dengue virus-specific antibodies, types IgG and
IgM, can be useful in confirming a diagnosis in the later
stages of the infection. Both IgG and IgM are produced
after 5–7 days.
The highest levels (titres) of IgM are detected following
a primary infection, but IgM is also produced in
secondary and tertiary infections. IgM becomes
undetectable 30–90 days after a primary infection, but
earlier following re-infections.
IgG, by contrast, remains detectable for over 60 years
and, in the absence of symptoms, is a useful indicator of
past infection.
After a primary infection IgG reaches peak levels in the
blood after 14–21 days. Both IgG and IgM provide
protective immunity to the infecting serotype of the virus.
The detection of IgG alone is not considered diagnostic
unless blood samples are collected 14 days apart and a
greater than fourfold increase in levels of specific IgG is
detected. In a person with symptoms, the detection of IgM
is considered diagnostic.
PREVENTION
There are no approved vaccines for the dengue virus.
Prevention thus depends on control of and protection from
the bites of the mosquito that transmits it.
The primary method of controlling A. aegypti is by
eliminating its habitats. This is done by emptying containers
of water or by adding insecticides or
biological control agents to these areas, although spraying
with organophosphate or pyrethroid insecticides is not
thought to be effective.
People can prevent mosquito bites by wearing clothing that
fully covers the skin, using mosquito netting while resting,
and/or the application of insect repellent (DEET being the
most effective).
Lays its eggs in clean, stagnant water
• Pots, pans and utensils
MANAGEMENT
There are no specific antiviral drugs for dengue, however
maintaining proper fluid balance is important. Treatment
depends on the symptoms, varying from
oral rehydration therapy at home with close follow-up, to
hospital admission with administration of
intravenous fluids and/or blood transfusion. A decision for
hospital admission is typically based on the presence of
the "warning signs" listed in the table above, especially in
those with preexisting health conditions.
Intravenous hydration is usually only needed for one or
two days. The rate of fluid administration is titrated to a
urinary output of 0.5–1 mL/kg/hr, stable vital signs and
normalization of hematocrit.
Invasive medical procedures such as nasogastric intubation,
intramuscular injections and arterial punctures are avoided, in view of
the bleeding risk
Paracetamol (acetaminophen) is used for fever and discomfort while
NSAIDs such as ibuprofen and aspirin are avoided as they might
aggravate the risk of bleeding
Blood transfusion is initiated early in patients presenting with unstable
vital signs in the face of a decreasing platelets count. Actually the
whole blood are recommended, while platelets and fresh frozen plasma
are usually not.
During the recovery phase intravenous fluids are discontinued to
prevent a state of fluid overload. If fluid overload occurs and vital signs
are stable, stopping further fluid may be all that is needed. If a person
is outside of the critical phase, a loop diuretic such as furosemide may
be used to eliminate excess fluid from the circulation

Dengue fever is a mosquito-borne viral infection that causes high fever, severe headache, muscle and joint pain, and rash.

  • 1.
  • 2.
    INTRODUCTION Dengue fever ,also known as breakbone fever, is an infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases the disease develops into the life-threatening dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs
  • 3.
    Dengue is transmittedby several species of mosquito within the genus Aedes, principally A. aegypti. The virus has four different SERO types; infection with one type usually gives lifelong immunity to that type, but only short-term immunity to the others. Subsequent infection with a different type increases the risk of severe complications. As there is no commercially available vaccine, prevention is sought by reducing the habitat and the number of mosquitoes and limiting exposure to bites.
  • 4.
    Treatment of acutedengue is supportive, using either oral or intravenous rehydration for mild or moderate disease, and intravenous fluids and blood transfusion for more severe cases. Apart from eliminating the mosquitoes, work is ongoing on a vaccine, as well as medication targeted directly at the virus.
  • 5.
  • 6.
    Typically, people infectedwith dengue virus are asymptomatic (80%) or only have mild symptoms such as an uncomplicated fever. Others have more severe illness (5%), and in a small proportion it is life-threatening. The incubation period (time between exposure and onset of symptoms) ranges from 3–14 days, but most often it is 4–7 days. Therefore, travelers returning from endemic areas are unlikely to have dengue if fever or other symptoms start more than 14 days after arriving home. Children often experience symptoms similar to those of the common cold and gastroenteritis (vomiting and diarrhea) and have a greater risk of severe complications, though initial symptoms are generally mild but include high fever.
  • 8.
    SYMPTOMS OF DENGUE: The characteristicsymptoms of dengue are sudden-onset fever, headache (typically located behind the eyes), muscle and joint pains, and a rash. The alternative name for dengue, "breakbone fever", comes from the associated muscle and joint pains. The course of infection is divided into three phases: febrile, critical, and recovery.
  • 9.
  • 10.
    The febrile phaseinvolves high fever, often over 40 °C (104 °F), and is associated with generalized pain and a headache; this usually lasts two to seven days. Vomiting may also occur. A rash occurs in 50–80% of those with symptoms in the first or second day of symptoms as flushed skin, or later in the course of illness (days 4–7), as a measles-like rash. Some petechiae (small red spots that do not disappear when the skin is pressed, which are caused by broken capillaries) can appear at this point, as may some mild bleeding from the mucous membranes of the mouth and nose.
  • 11.
  • 12.
    In some people,the disease proceeds to a critical phase. During this phase there may be significant fluid accumulation in the chest and abdominal cavity due to increased capillary permeability and leakage. This leads to depletion of fluid from the circulation and decreased blood supply to vital organs. During this phase, organ dysfunction and severe bleeding, typically from the gastrointestinal tract, may occur. Shock (dengue shock syndrome) and hemorrhage (dengue hemorrhagic fever) occur in less than 5% of all cases of dengue, however those who have previously been infected with other serotypes of dengue virus ("secondary infection") are at an increased risk. This critical phase, while rare, occurs relatively more commonly in children and young adults.
  • 13.
  • 14.
    The recovery phaseoccurs next, with resorption of the leaked fluid into the bloodstream. This usually lasts two to three days. The improvement is often striking, but there may be severe itching and a slow heart rate. Another rash may occur with either a maculopapular or a vasculitic appearance, which is followed by. peeling of the skin. During this stage, a fluid overload state may occur; if it affects the brain, it may cause a reduced level of consciousness or seizures. A feeling of fatigue may last for weeks in adults.
  • 15.
  • 16.
    Dengue fever virus(DENV) is an RNA virus of the family Flaviviridae; genus Flavivirus. Most are transmitted by arthropods (mosquitoes or ticks), and are therefore also referred to as arboviruses (arthropod-borne viruses). The dengue virus genome (genetic material) contains about 11,000 nucleotide bases, which code for the three different types of protein molecules (C, prM and E) that form the virus particle and seven other types of protein molecules (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5) that are only found in infected host cells and are required for replication of the virus. There are four strains of the virus, which are called serotypes, and these are referred to as DENV-1, DENV-2, DENV-3 and DENV-4.
  • 17.
  • 18.
    Dengue virus isprimarily transmitted by Aedes mosquitoes, particularly A. aegypti. They typically bite during the day, particularly in the early morning and in the evening. Humans are the primary host of the virus, but it also circulates in nonhuman primates. An infection can be acquired via a single bite. A female mosquito that takes a blood meal from a person infected with dengue fever becomes itself infected with the virus in the cells lining its gut. About 8–10 days later, the virus spreads to other tissues including the mosquito's salivary glands and is subsequently released into its saliva.
  • 19.
    The virus seemsto have no detrimental effect on the mosquito, which remains infected for life. Aedes aegypti prefers to lay its eggs in artificial water containers, to live in close proximity to humans, and to feed on people rather than other vertebrates. Dengue can also be transmitted via infected blood products and through organ donation Vertical transmission (from mother to child) during pregnancy or at birth has been reported
  • 20.
    1. Eggs 2. Larvae 3.Pupae 4. Adult LIFE CYCLE OF AEDES AEGYPTI
  • 21.
    TRANSMISSION CYCLE -1 Transmission from human to human requires the same female mosquito to bite a viremic human and then bite a susceptible human at an interval of around 10-12 days
  • 22.
    TRANSMISSION CYCLE -2 Cycle in the mosquito
  • 23.
    TRANSMISSION CYCLE -3 Viremia Extrinsic Incubation period Intrinsic Incubation period Viremia
  • 24.
  • 25.
    When a mosquitocarrying dengue virus bites a person, the virus enters the skin together with the mosquito's saliva. It binds to and enters white blood cells, and reproduces inside the cells while they move throughout the body. The white blood cells respond by producing a number of signaling proteins, such as cytokines and interferons, which are responsible for many of the symptoms, such as the fever, the flu-like symptoms and the severe pains. In severe infection, the virus production inside the body is greatly increased, and many more organs (such as the liver and the bone marrow) can be affected, and fluid from the bloodstream leaks through the wall of small blood vessels into body cavities.
  • 26.
    As a result,less blood circulates in the blood vessels, and the blood pressure becomes so low that it cannot supply sufficient blood to vital organs. Furthermore, dysfunction of the bone marrow leads to reduced numbers of platelets, which are necessary for effective blood clotting; this increases the risk of bleeding, the other major complication of dengue fever.
  • 27.
  • 28.
    WARNING SIGNS Worsening abdominalpain Ongoing vomiting Liver enlargement Mucosal bleeding High hematocrit with low platelets Lethargy or restlessness Serosal effusions
  • 29.
    The diagnosis ofdengue is typically made clinically, on the basis of reported symptoms and physical examination; However, early disease can be difficult to differentiate from other viral infections. A probable diagnosis is based on the findings of fever plus two of the following: nausea and vomiting, rash, generalized pains, low white blood cell count, positive tourniquet test, or any warning sign in someone who lives in an endemic area.
  • 30.
    Dr.T.V.Rao MD 30 HOW TODO 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.
  • 31.
    The earliest changedetectable on laboratory investigations is a low white blood cell count, which may then be followed by low platelets with moderately elevated level of aminotransferase In severe disease, plasma leakage results in hemoconcentration (as indicated by a rising hematocrit) and hypoalbuminemia. Pleural effusions or ascites can be detected by physical examination when large, but the demonstration of fluid on ultrasound may assist in the early identification of dengue shock syndrome. Dengue shock syndrome occurs if pulse pressure drops to ≤ 20 mm Hg while peripheral vascular collapse is evidenced.
  • 32.
    FOUR CRITERIA FOR DHF Fever,last for 2-7days at least one of Hemorrhage evidences Thrombocytopenia :PLT<100,000/mm3 Evidence of plasma leakage: • a rise in Hct: >=20% • pleural effusion ,ascites and hypoprotinemia
  • 33.
  • 35.
    Dengue fever maybe diagnosed by microbiological laboratory testing. This can be done by virus isolation in cell cultures, nucleic acid detection by PCR, viral antigen detection (such as for NS1 i.e. non structural protein test detect antigen on 1st day of attack) or specific antibodies (serology). All tests may be negative in the early stages of the disease. PCR and viral antigen detection are more accurate in the first seven days. Tests for dengue virus-specific antibodies, types IgG and IgM, can be useful in confirming a diagnosis in the later stages of the infection. Both IgG and IgM are produced after 5–7 days.
  • 36.
    The highest levels(titres) of IgM are detected following a primary infection, but IgM is also produced in secondary and tertiary infections. IgM becomes undetectable 30–90 days after a primary infection, but earlier following re-infections.
  • 37.
    IgG, by contrast,remains detectable for over 60 years and, in the absence of symptoms, is a useful indicator of past infection. After a primary infection IgG reaches peak levels in the blood after 14–21 days. Both IgG and IgM provide protective immunity to the infecting serotype of the virus. The detection of IgG alone is not considered diagnostic unless blood samples are collected 14 days apart and a greater than fourfold increase in levels of specific IgG is detected. In a person with symptoms, the detection of IgM is considered diagnostic.
  • 38.
  • 39.
    There are noapproved vaccines for the dengue virus. Prevention thus depends on control of and protection from the bites of the mosquito that transmits it. The primary method of controlling A. aegypti is by eliminating its habitats. This is done by emptying containers of water or by adding insecticides or biological control agents to these areas, although spraying with organophosphate or pyrethroid insecticides is not thought to be effective. People can prevent mosquito bites by wearing clothing that fully covers the skin, using mosquito netting while resting, and/or the application of insect repellent (DEET being the most effective).
  • 40.
    Lays its eggsin clean, stagnant water • Pots, pans and utensils
  • 41.
  • 42.
    There are nospecific antiviral drugs for dengue, however maintaining proper fluid balance is important. Treatment depends on the symptoms, varying from oral rehydration therapy at home with close follow-up, to hospital admission with administration of intravenous fluids and/or blood transfusion. A decision for hospital admission is typically based on the presence of the "warning signs" listed in the table above, especially in those with preexisting health conditions. Intravenous hydration is usually only needed for one or two days. The rate of fluid administration is titrated to a urinary output of 0.5–1 mL/kg/hr, stable vital signs and normalization of hematocrit.
  • 43.
    Invasive medical proceduressuch as nasogastric intubation, intramuscular injections and arterial punctures are avoided, in view of the bleeding risk Paracetamol (acetaminophen) is used for fever and discomfort while NSAIDs such as ibuprofen and aspirin are avoided as they might aggravate the risk of bleeding Blood transfusion is initiated early in patients presenting with unstable vital signs in the face of a decreasing platelets count. Actually the whole blood are recommended, while platelets and fresh frozen plasma are usually not. During the recovery phase intravenous fluids are discontinued to prevent a state of fluid overload. If fluid overload occurs and vital signs are stable, stopping further fluid may be all that is needed. If a person is outside of the critical phase, a loop diuretic such as furosemide may be used to eliminate excess fluid from the circulation