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

2. Introduction Dengue Fever Dengue Hemorrhagic Fever
Dengue Shock Syndrome

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

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

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

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

10. Antibody Structure

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
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
Dr S Guanasena

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

14. ? DHF a misnomer DLF

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
Dr. 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
Dr. 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
Dr. 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

19. Symptomatic to Asymptomatic Ratio
500:9500

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

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

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
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

26. Pulse Pressure Warning if 20 or below!
BP 120/60 Pulse Pressure =60
BP 80/60 Pulse Pressure= 20

27. DHF and DSS Not Complications of Dengue Fever
Dengue Hemorrhagic Fever < 5%- leak
Dengue Shock Syndrome-big leak

28. Capillary Refill Time

29. Dengue Shock Syndrome Profound Shock (No BP, No Pulse)
Decompensated Shock (feeble pulse, pulse pressure <20)
Compensated Shock (pulse pressure 20-30)

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

31. Convalescent Phase Lasts 5 – 7 days. Management: 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

32. Recovery

33. Misconceptions Platelet Transfusions Steroids
Misinterpretation of low WBC/TLC
Antibiotics
Growth Factors
Empiric Anti Malarials

34. Laboratory Diagnosis Epidemic/ Inter epidemic
Health care worker location (field worker vs tertiary care facility)

35. Dr. S Guanasena

36. Dr. 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
Dr. 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

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
1. IgM + in a single serum sample
2. IgG + in a single serum sample with a HI titre of or greater
Confirmed
Highly suggestive

41. IgM antibody to the secondary infecting DV serotype
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

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