1 of 42

1. Dengue – An Overview

Dengue Expert Advisory Group

1

2 of 42

Introduction

​

  • Dengue Fever
  • Dengue Hemorrhagic Fever
  • Dengue Shock Syndrome

2

3 of 42

3

4 of 42

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 of 42

Viral Serotypes

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

5

6 of 42

6

7 of 42

7

8 of 42

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 of 42

Pathogenesis of Dengue Fever

  • “Breakbone” symptoms due to adventitial and dendridic cell involvement of the marrow
  • Cytopenias due to direct marrow involvement

9

10 of 42

Antibody Structure

10

11 of 42

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 of 42

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 of 42

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

13

Dr. S Guanasena

14 of 42

? DHF a misnomer�DLF

14

15 of 42

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

​

15

Dr. S Guanasena

16 of 42

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

​

16

Dr. S Guanasena

17 of 42

Organ Involvement in Dengue

  • Direct involvement - infection of hepatocytes or brain with the dengue virus

​

  • Circulatory failure - poor organ perfusion

​

  • Drugs – Paracetamol

17

Dr. S Guanasena

18 of 42

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 of 42

Symptomatic to Asymptomatic Ratio

​

​

  • 500:9500

​

19

20 of 42

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 of 42

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 of 42

Tourniquet Test

22

23 of 42

Management Dengue Fever

  • Symptomatic

​

  • Monitoring

24 of 42

25 of 42

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

25

26 of 42

Pulse Pressure�Warning if 20 or below!

​

​

  • BP 120/60 Pulse Pressure =60
  • BP 80/60 Pulse Pressure= 20

26

27 of 42

DHF and DSS�Not Complications of Dengue Fever

​

  • Dengue Hemorrhagic Fever < 5%- leak

​

  • Dengue Shock Syndrome-big leak

27

28 of 42

Capillary Refill Time

28

29 of 42

Dengue Shock Syndrome

​

  • Profound Shock (No BP, No Pulse)

​

  • Decompensated Shock (feeble pulse, pulse pressure <20)

​

  • Compensated Shock (pulse pressure 20-30)

​

29

30 of 42

Suitable Fluids in DSS

  • Normal Saline
  • Hemaccel
  • 6% Starch
  • Dextran 40 in saline

30

31 of 42

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 of 42

Recovery

32

33 of 42

Misconceptions

​

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

33

34 of 42

Laboratory Diagnosis

  • Epidemic/ Inter epidemic

​

  • Health care worker location (field worker vs tertiary care facility)

34

35 of 42

35

Dr. S Guanasena

36 of 42

36

Dr. S Guanasena

37 of 42

Laboratory Diagnosis

  • Detection of Dengue viral antigen

​

  • Detection of the Dengue viral genome

​

  • Isolation of the Dengue virus

​

  • Detection of Dengue specific IgG, IgM

37

Dr. S Guanasena

38 of 42

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 of 42

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

​

​

​

Confirmed

​

​

Highly suggestive

39

40 of 42

40

41 of 42

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 of 42

  • The WHO does not recommend serologic tests by screening method

​

  • ELISA is the preferred mode

42