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1. Dengue – An Overview

1. Dengue – An Overview. Dengue Expert Advisory Group. Introduction. Dengue Fever Dengue Hemorrhagic Fever Dengue Shock Syndrome. Dengue Virus. Family : Flaviviridae Genus : Flavivirus Serotypes : DV1, DV2, DV3, DV4 Enveloped virus 3 major proteins SS positive sense RNA.

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1. Dengue – An Overview

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

  2. Introduction Dengue Fever Dengue Hemorrhagic Fever Dengue Shock Syndrome

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

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

  5. 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

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

  7. Antibody Structure

  8. 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

  9. 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

  10. 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

  11. ? DHF a misnomerDLF

  12. 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

  13. 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

  14. 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

  15. 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

  16. Symptomatic to Asymptomatic Ratio • 500:9500

  17. List of Warning SignsWarrants 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

  18. 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

  19. Tourniquet Test

  20. Management Dengue Fever • Symptomatic • Monitoring

  21. Pulse PressureWarning if 20 or below! BP 120/60 Pulse Pressure =60 BP 80/60 Pulse Pressure= 20

  22. DHF and DSSNot Complications of Dengue Fever Dengue Hemorrhagic Fever < 5%- leak Dengue Shock Syndrome-big leak

  23. Capillary Refill Time

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

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

  26. 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

  27. Recovery

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

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

  30. Dr. S Guanasena

  31. Dr. S Guanasena

  32. 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

  33. 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

  34. Laboratory diagnostic criteria Highly suggestive Confirmed 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

  35. 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

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

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