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

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Presentation on theme: "1. Dengue – An Overview Dengue Expert Advisory Group 1."— Presentation transcript:

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

2 Introduction Dengue Fever Dengue Hemorrhagic Fever Dengue Shock Syndrome 2

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

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

10 Antibody Structure 10

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 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 cross1. Are less effective reacting T cellsin 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 14

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 18

19 Symptomatic to Asymptomatic Ratio 500:9500 19

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 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 DHFConfirmed 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

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

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

28 Capillary Refill Time 28

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

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

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 31

32 Recovery 32

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

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

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 7 th 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 39

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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 42

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