Dengue

1. Dengue can be defined as a debilitating viral disease of
the tropics and subtropics that gets transmitted by
mosquitoes, and causing sudden fever and acute pains
in the joints.

3. Dengue:
• Infection of tropical and subtropical regions
• Nonspecific febrile illness to fatal hemorrhagic
disease
• Infection caused by 4 closely related virus and spread
by an insect vector – Aedes mosquito

4. Dengue virus
• Flavi viruses: RNA
• Arbovirus group
• 4 serotypes – DENV 1, DENV- 2, DENV-3, DENV-4
• Cycle involves humans and mosquitos
• Infection with one virus gives immunity to that specific serotype
only

5. Vector for Dengue
• Aedes aegypti, Aedes albopictus less commonly
• Domestic day biting mosquito
• Prefers to feed on humans
• Breeds in stored clean water
• Have short flight range
• May bite several people in same household

6. Dengue: History
• It is said that the four serotypes of virus were
originated from monkeys and then transmit to
humans in Southeast Asia and some parts of Africa
about 100 - 800 years ago
• First reported epidemics in 1779 –80 in Asia, Africa
and North America.
• Until the second world war, DF was restricted to
some countries of the world (Southeastern Asia
and Africa)
• But with beginning of the 2nd world war,
transportation of Aedes mosquitoes by cargo could
play an important factor for dissemination of the
viruses around the world.

7. •After World War II, pandemic of dengue which began in
Southeast Asia and Africa, expanded geographical
distribution and then epidemics with multiple serotypes and
emergence of DHF starts globally
•Epidemics every 10-40 years due to introduction of new
serotype
•In 1980s a second re-expansion of DHF in Asia with
epidemics in India, Sri Lanka and Maldives, Taiwan, PRC;
Africa and Americas

8. Dengue: Current Global Scenario
• Climate changes can have a significant effect on the
incidence and prevalence rate of Dengue infection.
• Progressively larger epidemics
• Primarily affects urban areas
• In many of tropical and subtropical countries, dengue
is endemic and disease occurs every year, when
rainfall is optimal for breeding
• Now, dengue is endemic in at least 100 countries in
Asia (more in South-east), Africa, the Americas, and
the Caribbean islands.

9. Reasons for resurgence
• Uncontrolled urbanization and population growth
 substandard housing, inadequate water, sewer
and waste management
• Deterioration of public health infrastructure
• Dengue fever is one of the most rapidly emerging
infectious diseases in the world, and due to faster
international and domestic air travel it continues
to spread as a travel-related infection.
• Ineffective mosquito control in endemic regions
• Hyperendemicity: prevalence of multiple
serotypes

10. Dengue in India
• First isolated in Calcutta in 1945
• Extensive epidemics since 1963
• DHF, DSS epidemics over last 4 decades
• Severe epidemic in Delhi in 1996,
2006,2012,2019; In Lucknow in 1998,
2003, 2006
• All 4 serotypes are prevalent
• Viruses prevalent all over except
Himalayan region & Kashmir

11. Dengue Fever : Clinical
Features
• Incubation period 2-7 days
• Sudden fever 40 degree Celsius -41 degree Celsius
• Nonspecific constitutional symptoms
• Severe muscle aches, retro-orbital pain
• Hepatomegaly
• Rash
• Facial flush
• Fever subsides in 2-7 days, may be biphasic

12. Laboratory findings in Dengue
• CBC: Thrombocytopenia
• HIA (Hemagglutinin Inhibition assay): test antibody against
hemagglutinin spike of virus.
• FAT (Fluorescence antibody test): detects virus antigen using
virus specific antibody
• MAC-ELISA (IgM capture ELISA): detects Dengue specific IgM
antibody.it can distinguish primary infection from secondary
infection. In primary infection ratio of IgM to IgG is greater
than 1.5
• Neutralization test: detect antibody against dengue
• Virus isolation: mosquito cell line culture with patient serum.
• Nucleic acid detection: RT-PCR is used to detect virus

13. DDx
• Respiratory Infections
• Measles
• Rubella (German measles)
• Malaria
• Meningoencephalitis
• Pyelonephritis
• Septicemia

14. WHO case definition for DF:
Acute Febrile illness with 2 or > of the
following:
• Headache
• Retro-orbital pain
• Myalgia
• Arthralgia
• Rash
• Hemorrhagic manifestations
• Leukopenia
• Hepatomegaly common

15. Pathogenesis of dengue fever
•Dengue virus after entering in the body invades the local macrophages and
multiply there.
•Infected local cells then migrate from site of infection to lymph nodes,
where monocytes and macrophages are recruited, which become targets of
infection.
•Consequently, infection is amplified and virus is disseminated through the
lymphatic system. As a result of this primary viremia, several cells of the
mononuclear lineage, including blood-derived monocytes
•Viremia develops within 24 hours. During this period, virus travels
throughout the body.
•Bone marrow cells have also been shown to be susceptible to infection with
DENV
•In severe case, viral load is very high and many vital organs are affected.
•Virus infected macrophages produces a number of signaling proteins such as
interferons, cytokines, chemokines, TNF, other mediators which are
responsible for many symptoms such as flue like syndrome and pain.

16. •These mediators affects hemostatic system of body.
•Fluid from blood vessels starts to leak out so that the blood volume
decreases resulting in low blood pressure.
•Decrease in blood pressure causes insufficient supply of blood and
Oxygen to vital organs such as brains.
•Dengue also infects bone marrow, so that bone marrow cannot
produces sufficient platelets.
•Since platelets are needed for blood clotting, dengue infection causes
blood clotting defect and increase the risk of bleeding.

17. Types of Dengue infection
Primary infection:
•Primary infection is characterized by fever, break bone fever, retro-
orbital pain and flue like syndrome.
•The person who is not previously infected with any Flavivirus is termed
as primary infection.
•In primary infection ratio of Dengue specific IgM to IgG is high.
Secondary infection:
•Dengue infection in host who is immunologically sensitized to dengue
or other flavivirus is termed as secondary infection.
•Secondary infection is characterized by rise in antibody titer. The ratio
of IgM to IgG is low.

18. Symptomatic dengue includes, classical dengue fever, Dengue
haemorrhagic fever (DHF) and Dengue shock syndrome (DSS).
I. Classical dengue fever:
• It is characterized by fever, rashes, severe headache, pain
behind eyes, pain in muscle and joints, enlarged lymph
nodes,
• Fever lasts for 2-7 days
• Myalgia and break bone fever ( deep bone pain) is the
characteristic of Dengue fever
• Classical dengue fever is self-limited.
• Mostly adults and older children are affected

19. II. Dengue hemorrhagic fever (DHF):
•DHF is marked by bleeding from skin and mucus membrane.
•DHF has four major clinical manifestation- High fever,
hemorrhagic phenomenon, hepatomegaly and circulatory failure.
•In early stage of infection DHF resembles classical dengue fever.
•Usually occurs in children
•About 23% of children with DHF develops circulatory failure
with haemo-concentration and a marked decrease in platelets
counts leading to severe hemorrhage.

20. DHF: Pathogenesis
• Secondary infection with another serotype leads
to ‘antibody mediated enhancement’
• Heterotypic antibodies are non protective and fail
to neutralize the virus
• Virus-antibody complexes taken up by monocytes
• Virion multiplication in human monocytes is
promoted
• Activation of CD4+ and CD8+ lymphocytes 
release of cytokines
• Complement system activated with depression of
C3 & C5

21. Hypothesis on Pathogenesis
of DHF
 In a subsequent infection, the pre-existing
heterologous antibodies form complexes with
the new infecting virus serotype, but do not
neutralize the new virus

22. Hypothesis on Pathogenesis
of DHF (Part 3)
 Antibody-dependent enhancement is the
process in which certain strains of dengue
virus, complexed with non-neutralizing
antibodies, can enter a greater proportion of
cells of the mononuclear lineage, thus
increasing virus production

23. DHF: Pathophysiology
 Activation of complement  Increased vascular
permeability loss of plasma from vascular
compartment  hemoconcentration & shock
 Disorder of haemostasis involving thrombocytopenia,
vascular changes and coagulopathy
 Severe DHF with features of shock : DSS

24. DHF: WHO Criteria for diagnosis
Often occurs with defervescence of fever, swelling
All of the following must be present:
 Fever
 Hemorrhagic tendencies:
 +ve tourniquet test
 Petichiae, ecchymosis or purpura
 Bleeding from other sites
 Thrombocytopenia (<=100,000/cu mm)
 Evidence of plasma leak
 Rise in hematocrit > 20% above average
 Drop in Hct
 Pleural effusion/ascites/hypoproteinemia

25. III. Dengue shock syndrome (DSS):
•DSS is serious form of DHF.
•All serotypes of Dengue are associated with DHF and DSS.
•The cause of DSS is not clearly understood. But it is assumed due to
antibody dependent enhancement (ADE).
•Pre-existing heterologous antibody against particular dengue
serotype binds with the new infected virus serotype by its Fab region
and Fc region of antibody binds to receptor on macrophage. So this
pre-existing antibody increases virus infection to healthy
macrophages.
•From recent outbreak information of DHF, patients infected with
DEN-2 after primarily infected with other serotypes can leads to DSS.
•DSS is characterized by circulatory failure, rapid pulse, abnormal
pain, severe bleeding from GI tract and other organs.
•Usually occurs in children

26. DSS: WHO Criteria for
diagnosis
All of the above + evidence of circulatory failure:
 Rapid, weak pulse
 Narrow pulse pressure < =20 mm hg
 Cold clammy skin
 Restlessness
Often present with abdominal pain; mistaken for acute
abdominal emergency

27. Grading of DV infection
DF/DHF Grade Symptoms Lab
DF Fever with 2 or > of: headache/retro-orbital
pain, myalgia, arthralgia
Leukopenia,
occasionally
thrombocytopenia,
no evidence of
plasma leak
DHF I Above symptoms + Positive tourniquet
test
Platelets < 100,000,
Hct rise > 20%
DHF II Above symptoms + spontaneous
bleeding
,,
DHF III/DSS Above symptoms + symptoms of
circulatory failure
,,
DHF IV/DSS Profound shock with undetectable BP and
pulse
,,

28. WHO Lab Criteria for Dengue
infection:
• Probable Case:
o CF + Supportive Serology: Acute HI titre >
1280, comparable IgG ELISA or +ve IgM
o or occurrence at same location & time as
other confirmed cases
• Confirmed case:
o isolation of virus from serum/ autopsy
specimen
o Demonstration of dengue virus antigen in
serum/ CSF/ Autopsy tissue
o Detection of dengue virus genome by PCR

29. Management: DF
• No specific Tt
• Analgesics/antipyretics
• Avoid agents which may impair platelet function eg
aspirin

30. Management: DHF:
• Hospitalize
• Closely monitor for shock; repeated hematocrit
measurements
• If Hct rising by >20%, IV fluids as 5% deficit
• Start with DNS 6-7 ml/kg/hr.
• Improves  reduce gradually over 24-48 hrs.
• No improvement   upto 15 ml/kg/hr  colloid
solution

31. Revised WHO classification (2009)
Probable dengue Warning signs Severe dengue
Live in/travel to endemic area Abdominal pain or tenderness Severe plasma leak
Fever + 2 of : Persistent vomiting Shock
Nausea, vomiting Clinical fluid accumulation Fluid accumulation with
respiratory distress
Rash Lethargy/ restlessness Severe bleeding
Aches & pains Liver enlargement > 2 cm Severe organ involvement
Tourniquet test +ve Laboratory increase in HCT
concurrent with rapid decrease
in platelet count
Liver ALT or AST >=1000
Leucopenia Impaired consciousness
Any warning sign Heart or other organs

32. Prevention
 1. Anti-mosquito measures
 Avoid open stagnant water in and
around home
 Bed nets
 Long sleeved clothing
 In house spraying
 Mosquito repellants

33. 2. Dengue vaccine
•Dengvaxia vaccine is licensed and available in some
countries for people ages 9-45 years old. The World Health
Organization recommends that the vaccine only be given to
persons with confirmed prior dengue virus infection.
•The vaccine manufacturer, Sanofi Pasteur, announced in
2017 that people who receive the vaccine and have not
been previously infected with a dengue virus may be at risk
of developing severe dengue if they get dengue after being
vaccinated.