1. Dengue is caused by four related viruses and presents as dengue fever or the more severe dengue hemorrhagic fever and dengue shock syndrome. 2. The virus infects blood macrophages and causes an immune response that is protective only against the infecting serotype. A secondary infection by a different serotype increases the risk of severe disease. 3. Severe disease is thought to be caused by antibody-dependent enhancement where cross-reactive antibodies from a previous infection facilitate infection of monocytes and endothelial cells, resulting in increased viral replication and cytokine release. This leads to plasma leakage and bleeding manifestations.

1. 1. Dengue – An Overview
Dengue Expert Advisory Group
1

2. Introduction
• Dengue Fever
• Dengue Hemorrhagic Fever
• Dengue Shock Syndrome
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3. 3

4. Dengue Virus
• Family : Flaviviridae
• Genus : Flavivirus
• Serotypes : DV1, DV2, DV3, DV4
• Enveloped virus
• 3 major proteins
• SS positive sense RNA
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Dr. S Guanasena

5. Viral Serotypes
• DV1
• DV2
• DV3
• DV4
• Subgroups and clades
• One or more virus types in circulation
during an epidemic
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6. 6

7. 7

8. 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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9. 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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10. Antibody Structure
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11. 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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Dr. S Guanasena

12. 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
12
Dr S Guanasena

13. Cytokines secreted from infected
macrophages and endothelial
cells
Pathogenesis of Leak
Cytokines secreted from
activated T cells
Exaggerated Cytokine response
Endothelial dysfunction
DV specific antibody interact with
the endothelium
DV infects endothelium
and kills cells
13Dr. S Guanasena

14. ? DHF a misnomer
DLF
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15. 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
15Dr. S Guanasena

16. 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 16Dr. S Guanasena

17. Organ Involvement in Dengue
• Direct involvement - infection of hepatocytes
or brain with the dengue virus
• Circulatory failure - poor organ perfusion
• Drugs – Paracetamol
17Dr. S Guanasena

18. 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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19. Symptomatic to Asymptomatic Ratio
• 500:9500
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20. 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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21. 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

22. Tourniquet Test
22

23. Management Dengue Fever
• Symptomatic
• Monitoring

25. Highly Suggestive of DHF Confirmed DHF**
• Disproportionate tachycardia
• Narrowing of pulse pressure < 20
mm
• CRFT > 2 secs
• 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
• Ascites on U/S
• Pleural effusions (CXR Right lateral
decubitus or chest U/S to detect
minimal effusion)
** Definitive evidence of plasma leakage
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26. Pulse Pressure
Warning if 20 or below!
• BP 120/60 Pulse Pressure =60
• BP 80/60 Pulse Pressure= 20
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27. DHF and DSS
Not Complications of Dengue Fever
• Dengue Hemorrhagic Fever < 5%- leak
• Dengue Shock Syndrome-big leak
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28. Capillary Refill Time
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29. 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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30. Suitable Fluids in DSS
• Normal Saline
• Hemaccel
• 6% Starch
• Dextran 40 in saline
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31. 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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32. Recovery
32

33. Misconceptions
• Platelet Transfusions
• Steroids
• Misinterpretation of low WBC/TLC
• Antibiotics
• Growth Factors
• Empiric Anti Malarials
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34. Laboratory Diagnosis
• Epidemic/ Inter epidemic
• Health care worker location (field worker
vs tertiary care facility)
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35. 35Dr. S Guanasena

36. 36Dr. S Guanasena

37. Laboratory Diagnosis
• Detection of Dengue viral antigen
• Detection of the Dengue viral genome
• Isolation of the Dengue virus
• Detection of Dengue specific IgG, IgM
37Dr. S Guanasena

38. 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 38

39. Laboratory diagnostic criteria
One of the following:
1. PCR + NS1 +
2. Virus culture +
3. IgM seroconversion in
paired sera
4. IgG seroconversion in
paired sera or fourfold
IgG titer increase in
paired sera
One of the following:
1. IgM + in a single serum
sample
2. IgG + in a single serum
sample with a HI titre of
1280 or greater
ConfirmedHighly suggestive
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40. 40

41. 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)
41
Dr. S Guanasena

42. • The WHO does not recommend serologic
tests by screening method
• ELISA is the preferred mode
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