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Dengue – An Overview

Dengue Expert Advisory Group

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 Introduction

• Dengue Fever
• Dengue Hemorrhagic Fever
• Dengue Shock Syndrome

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 Dengue Virus

• Family : Flaviviridae
• Genus : Flavivirus
• Serotypes : DV1, DV2, DV3, DV4

• Enveloped virus
• 3 major proteins
• SS positive sense RNA

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 Viral Serotypes
• DV1
• DV2
• DV3
• DV4
• Subgroups and clades
• One or more virus types in circulation
during an epidemic

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 Pathogenesis
• Virus enters blood-reticuloendothelial
system and bone marrow-blood
• Incubation period 3-10 days
• Viremia for 7 days after the entry
• Immune response ONLY for the infecting
serotype

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Pathogenesis of Dengue Fever
• “Breakbone” symptoms due to adventitial
and dendridic cell involvement of the
marrow
• Cytopenias due to direct marrow
involvement

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Antibody Structure

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 Pathogenesis of DHF – Role of cross
reactive DV antibodies
Cross reactive antibody binds to the infecting virus

Form v- ab complexes.
V- ab complexes attach to cells bearing receptors for the Fc portion of the ab

Facilitates entry of the virus into these cells and the viral replication. Therefore,
more cells are infected

Increased immune response & release of cytokines

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 Pathogenesis of DHF
Role of cross reactive T cells
Cross reactive T cells reacts with dengue virus
of subsequent infection. Causes activation of
these T cells

Activated cross 1. Are less effective

reacting T cells in eliminating the
secondary infecting
DV

2. T cell activation
contribute to disease
pathogenesis

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 Cytokines secreted from infected Pathogenesis of Leak
macrophages and endothelial Cytokines secreted from
cells activated T cells

Exaggerated Cytokine response

DV specific antibody interact with DV infects endothelium

the endothelium and kills cells

Endothelial dysfunction

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? DHF a misnomer
DLF

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 Thrombocytopenia
• Low production due to temporary bone marrow
suppression (DV infection, effect of cytokines)

• Increased consumption (activation of coagulation

system, DIC)

• Direct infection of platelets with the virus: kills

platelets

• Increased destruction of platelets by activated

macrophages

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 Bleeding
• Thrombocytopenia

• Activation of the coagulation system due to

endothelial dysfunction, cytokines

• Disseminated intravascular coagulation

• Poor perfusion of GIT: can lead to mucosal

bleeding

• Drugs: Steroids, NSAIDS

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 Organ Involvement in Dengue

• Direct involvement - infection of hepatocytes

or brain with the dengue virus

• Circulatory failure - poor organ perfusion

• Drugs – Paracetamol

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 Organ Involvement
• Like other viruses many organ
involvement has been reported (myositis,
pancreatitis, myocarditis etc.)
• GB syndrome
• Stevens Johnsons
• Features may vary from one year to
another and one epidemic to another

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 Symptomatic to Asymptomatic Ratio

• 500:9500

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 List of Warning Signs
Warrants Admission
• No clinical improvement / worsening clinical
parameters
• Persistent vomiting
• Severe abdominal pain
• Lethargy and or restlessness
• Bleeding: severe epistaxis, black stools,
hematemesis, extensive menstrual bleeding,
hematuria
• Giddiness
• Pale cold clammy extremities
• Less / no urine output for 4 – 6 hours

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 Clinical Features – DF
• Fever > 2 and < 10 days (essential criterion)
• Headache
• Retro orbital pain
• Myalgia
• Arthralgia/ severe backache/ bone pains
• Rash
• Bleeding manifestations (epistaxis, hematemesis, bloody
stools, menorrhagia, hemoptysis)
• Abdominal pain
• Decreased urinary output despite adequate fluid intake
• Irritability in infants
Tourniquet Test

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 Management Dengue Fever
• Symptomatic

• Monitoring
Highly Suggestive of DHF
 Disproportionate tachycardia
 Narrowing of pulse pressure < 20
mm
 CRFT > 2 secs
 Tender hepatomegaly (DHF likely)
Confirmed DHF**
 Ascites on U/S
 Pleural effusions (CXR Right lateral
decubitus or chest U/S to detect
minimal effusion)
** Definitive evidence of plasma leakage

 Haemoconcentration
HCT 20% rise from baseline or rise
approaching 20% if patient already
on IV fluids
 Biochemistry
o Serum albumin < 3.5 g/dl or 0.5
gm/dl fall during illness
 Non fasting serum cholesterol < 100
mg/dl or 20mg/dl fall during illness
 Oedematous gall bladder wall on U/S
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 Pulse Pressure
Warning if 20 or below!

• BP 120/60 Pulse Pressure =60

• BP 80/60 Pulse Pressure= 20

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 DHF and DSS
Not Complications of Dengue Fever

• Dengue Hemorrhagic Fever < 5%- leak

• Dengue Shock Syndrome-big leak

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Capillary Refill Time

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 Dengue Shock Syndrome

• Profound Shock (No BP, No Pulse)

• Decompensated Shock (feeble pulse,

pulse pressure <20)

• Compensated Shock (pulse pressure 20-

30)
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 Suitable Fluids in DSS
• Normal Saline
• Hemaccel
• 6% Starch
• Dextran 40 in saline

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 Convalescent Phase
• Lasts 5 – 7 days.
– Good appetite
– Convalescent rash
– Pruritus
– Heamodynamic stability
– Bradycardia
– Diuresis
– Stabilization of HCT
– Rise in WBC
– Rise in platelet count.
• Management:
– Maintain oral intake, antihistamines, rest,
discharge
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Recovery

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 Misconceptions

• Platelet Transfusions
• Steroids
• Misinterpretation of low WBC/TLC
• Antibiotics
• Growth Factors
• Empiric Anti Malarials

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 Laboratory Diagnosis
• Epidemic/ Inter epidemic

• Health care worker location (field worker

vs tertiary care facility)

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 Laboratory Diagnosis

• Detection of Dengue viral antigen

• Detection of the Dengue viral genome

• Isolation of the Dengue virus

• Detection of Dengue specific IgG, IgM

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 Dengue serology
• IgM detection (qualitative)
In a suspected case of dengue, presence of
dengue IgM indicates recent infection
IgM capture ELISA (blood collected after 5th day)
50% + in 3-5 day, 70% on 7th day, 100% day 10-14

• IgG detection (quantitative)

Diagnostic sero-conversion is defined as a four fold rise
(or fall) in antibodies in paired sera (collected in the
first 7 days & 10 – 14 days later)
HI assay / ELISA / Neutralization assay

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 Laboratory diagnostic criteria

Highly suggestive Confirmed

One of the following: One of the following:

1. IgM + in a single serum1. PCR + NS1 +
sample 2. Virus culture +
2. IgG + in a single serum3. IgM seroconversion in
sample with a HI titre of paired sera
1280 or greater 4. IgG seroconversion in
paired sera or fourfold
IgG titer increase in
paired sera 39
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 IgG antibody - specific to
the initial infecting DV
serotype + cross reacting
antibody

IgM antibody to the

secondary infecting DV
serotype

Following primary infection –

Specific antibody response + CMI (memory T cells)
Cross reactive antibody response + CMI (memory T cells)
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• The WHO does not recommend serologic
tests by screening method

• ELISA is the preferred mode

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