Download Dengue – An Overview

1. 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
Dr. S Guanasena
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Viral Serotypes
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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
Dr. S Guanasena
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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
reacting T cells
1. Are less effective
in eliminating the
secondary infecting
DV
2. T cell activation
contribute to disease
pathogenesis
Dr S Guanasena
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Pathogenesis of Leak
Cytokines secreted from infected
macrophages and endothelial
cells
Cytokines secreted from
activated T cells
Exaggerated Cytokine response
DV infects endothelium
and kills cells
DV specific antibody interact with
the endothelium
Endothelial dysfunction
Dr. S Guanasena
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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
Dr. S Guanasena
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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
Dr. S Guanasena
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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
Dr. S Guanasena
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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
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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
Confirmed DHF**


Disproportionate tachycardia
 Ascites on U/S
Narrowing of pulse pressure < 20
 Pleural effusions (CXR Right lateral
mm
decubitus or chest U/S to detect
 CRFT > 2 secs
minimal effusion)
** Definitive evidence of plasma leakage
 Tender hepatomegaly (DHF likely)
 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 2030)
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Suitable Fluids in DSS
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Normal Saline
Hemaccel
6% Starch
Dextran 40 in saline
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Convalescent Phase
• Lasts 5 – 7 days.
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Good appetite
Convalescent rash
Pruritus
Heamodynamic stability
Bradycardia
Diuresis
Stabilization of HCT
Rise in WBC
Rise in platelet count.
• Management:
– Maintain oral
discharge
intake,
antihistamines,
rest,
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Recovery
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Misconceptions
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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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Dr. S Guanasena
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Dr. S Guanasena
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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
Dr. S Guanasena
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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 1014
• 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 +
2. Virus culture +
sample
2. IgG + in a single serum3. IgM seroconversion in
sample with a HI titre of paired sera
4. IgG seroconversion in
1280 or greater
paired sera or fourfold
IgG titer increase in
paired sera
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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)
Dr. S Guanasena
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• The WHO does not recommend serologic
tests by screening method
• ELISA is the preferred mode
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