1. Dengue – An Overview
Dengue Expert Advisory Group
1
Introduction
• Dengue Fever
• Dengue Hemorrhagic Fever
• Dengue Shock Syndrome
2
3
Dengue Virus
• Family : Flaviviridae
• Genus : Flavivirus
• Serotypes : DV1, DV2, DV3, DV4
• Enveloped virus
• 3 major pro...
Viral Serotypes
• DV1
• DV2
• DV3
• DV4
• Subgroups and clades
• One or more virus types in circulation
during an epidemic...
6
7
Pathogenesis
• Virus enters blood-reticuloendothelial
system and bone marrow-blood
• Incubation period 3-10 days
• Viremia...
Pathogenesis of Dengue Fever
• “Breakbone” symptoms due to adventitial
and dendridic cell involvement of the
marrow
• Cyto...
Antibody Structure
10
Pathogenesis of DHF – Role of cross
reactive DV antibodies
Cross reactive antibody binds to the infecting virus
Form v- ab...
Pathogenesis of DHF
Role of cross reactive T cells
Cross reactive T cells reacts with dengue virus
of subsequent infection...
Cytokines secreted from infected
macrophages and endothelial
cells
Pathogenesis of Leak
Cytokines secreted from
activated ...
? DHF a misnomer
DLF
14
Thrombocytopenia
• Low production due to temporary bone marrow
suppression (DV infection, effect of cytokines)
• Increased...
Bleeding
• Thrombocytopenia
• Activation of the coagulation system due to
endothelial dysfunction, cytokines
• Disseminate...
Organ Involvement in Dengue
• Direct involvement - infection of hepatocytes
or brain with the dengue virus
• Circulatory f...
Organ Involvement
• Like other viruses many organ
involvement has been reported (myositis,
pancreatitis, myocarditis etc.)...
Symptomatic to Asymptomatic Ratio
• 500:9500
19
List of Warning Signs
Warrants Admission
• No clinical improvement / worsening clinical
parameters
• Persistent vomiting
•...
Clinical Features – DF
• Fever > 2 and < 10 days (essential criterion)
• Headache
• Retro orbital pain
• Myalgia
• Arthral...
Tourniquet Test
22
Management Dengue Fever
• Symptomatic
• Monitoring
Highly Suggestive of DHF Confirmed DHF**
• Disproportionate tachycardia
• Narrowing of pulse pressure < 20
mm
• CRFT > 2 s...
Pulse Pressure
Warning if 20 or below!
• BP 120/60 Pulse Pressure =60
• BP 80/60 Pulse Pressure= 20
26
DHF and DSS
Not Complications of Dengue Fever
• Dengue Hemorrhagic Fever < 5%- leak
• Dengue Shock Syndrome-big leak
27
Capillary Refill Time
28
Dengue Shock Syndrome
• Profound Shock (No BP, No Pulse)
• Decompensated Shock (feeble pulse,
pulse pressure <20)
• Compen...
Suitable Fluids in DSS
• Normal Saline
• Hemaccel
• 6% Starch
• Dextran 40 in saline
30
Convalescent Phase
• Lasts 5 – 7 days.
– Good appetite
– Convalescent rash
– Pruritus
– Heamodynamic stability
– Bradycard...
Recovery
32
Misconceptions
• Platelet Transfusions
• Steroids
• Misinterpretation of low WBC/TLC
• Antibiotics
• Growth Factors
• Empi...
Laboratory Diagnosis
• Epidemic/ Inter epidemic
• Health care worker location (field worker
vs tertiary care facility)
34
35Dr. S Guanasena
36Dr. S Guanasena
Laboratory Diagnosis
• Detection of Dengue viral antigen
• Detection of the Dengue viral genome
• Isolation of the Dengue ...
Dengue serology
• IgM detection (qualitative)
In a suspected case of dengue, presence of
dengue IgM indicates recent infec...
Laboratory diagnostic criteria
One of the following:
1. PCR + NS1 +
2. Virus culture +
3. IgM seroconversion in
paired ser...
40
IgG antibody - specific to
the initial infecting DV
serotype + cross reacting
antibody
IgM antibody to the
secondary infec...
• The WHO does not recommend serologic
tests by screening method
• ELISA is the preferred mode
42
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1. dengue an overview

  1. 1. 1. Dengue – An Overview Dengue Expert Advisory Group 1
  2. 2. Introduction • Dengue Fever • Dengue Hemorrhagic Fever • Dengue Shock Syndrome 2
  3. 3. 3
  4. 4. Dengue Virus • Family : Flaviviridae • Genus : Flavivirus • Serotypes : DV1, DV2, DV3, DV4 • Enveloped virus • 3 major proteins • SS positive sense RNA 4 Dr. S Guanasena
  5. 5. Viral Serotypes • DV1 • DV2 • DV3 • DV4 • Subgroups and clades • One or more virus types in circulation during an epidemic 5
  6. 6. 6
  7. 7. 7
  8. 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 8
  9. 9. Pathogenesis of Dengue Fever • “Breakbone” symptoms due to adventitial and dendridic cell involvement of the marrow • Cytopenias due to direct marrow involvement 9
  10. 10. Antibody Structure 10
  11. 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 11 Dr. S Guanasena
  12. 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. 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. 14. ? DHF a misnomer DLF 14
  15. 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. 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. 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. 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 18
  19. 19. Symptomatic to Asymptomatic Ratio • 500:9500 19
  20. 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 20
  21. 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. 22. Tourniquet Test 22
  23. 23. Management Dengue Fever • Symptomatic • Monitoring
  24. 24. 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 25
  25. 25. Pulse Pressure Warning if 20 or below! • BP 120/60 Pulse Pressure =60 • BP 80/60 Pulse Pressure= 20 26
  26. 26. DHF and DSS Not Complications of Dengue Fever • Dengue Hemorrhagic Fever < 5%- leak • Dengue Shock Syndrome-big leak 27
  27. 27. Capillary Refill Time 28
  28. 28. Dengue Shock Syndrome • Profound Shock (No BP, No Pulse) • Decompensated Shock (feeble pulse, pulse pressure <20) • Compensated Shock (pulse pressure 20- 30) 29
  29. 29. Suitable Fluids in DSS • Normal Saline • Hemaccel • 6% Starch • Dextran 40 in saline 30
  30. 30. 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 31
  31. 31. Recovery 32
  32. 32. Misconceptions • Platelet Transfusions • Steroids • Misinterpretation of low WBC/TLC • Antibiotics • Growth Factors • Empiric Anti Malarials 33
  33. 33. Laboratory Diagnosis • Epidemic/ Inter epidemic • Health care worker location (field worker vs tertiary care facility) 34
  34. 34. 35Dr. S Guanasena
  35. 35. 36Dr. S Guanasena
  36. 36. 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
  37. 37. 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
  38. 38. 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 39
  39. 39. 40
  40. 40. 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
  41. 41. • The WHO does not recommend serologic tests by screening method • ELISA is the preferred mode 42
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