Dengue

Question 1

What family does it belong to?

Answer 1

Flavivirus

Question 2

How many serotypes are there?

Answer 2

4

Question 3

Characteristics

Shape, envelope?, genome

Answer 3

Spherical, enveloped, single-stranded RNA genome

Question 4

What antigenic determinants does the envelope glycoprotein contain?

Answer 4

Group, subgroup, type specific

Question 5

What are the 3 manifestations of symptomatic infection?

Answer 5

1. Undifferentiated fever (infants and young children)
2. Dengue fever
3. Dengue haemorrhagic fever/Dengue shock syndrome

Question 6

Describe the infection and serotype linkage

Answer 6

1. First infection with any serotype
2. Subsequent infection with serotype different from that of first infection

Question 7

What does dengue fever cause?

Answer 7

• Abrupt onset of high fever
• Severe headache
• Pain behind eyes
• Muscle and joint pains
• Rash with islands of sparing

Question 8

What does Dengue Haemorrhagic Fever cause?

Answer 8

• Ascites (acute abdominal pain)
• Haemorrhagic manifestations, including at least a positive tourniquet test (petechia, purpura, ecchymosis, epistaxis, gum bleeding, haematemesis, melaena)
• Lab

Question 9

What is the clinical criteria of Dengue Shock Syndrome?

Answer 9

• Fever: acute onset, high, continuous lasting 2-7 days
• Haemorrhagic manifestations, including at least a positive tourniquet test (petechia, purpura, ecchymosis, epistaxis, gum bleeding, haematemesis, melaena)
• Hepatomegaly: enlargement of liver (maybe due to elevated liver enzymes)
• Frank hypertension: rapid and weak pulse with narrowing of pulse pressure/hypotension with presence of cold, clamy skin and restlessness
• Oliguria
• Lab

Question 10

What is the laboratory criteria of Dengue Haemorrhagic Fever/Shock Syndrome?

Answer 10

• Thrombocytopaenia (100000/mm3 or less)
• Haemoconcentration: haematocrit increased by 20% or more of recovery value
• Raised ALT/AST enzymes

Question 11

When does Dengue Shock Syndrome occur?

Answer 11

At time of/shortly after fall in temperature between day 3 and 7 of disease

Question 12

How long is the duration of shock of DSS?

will pt die or recover :0

Answer 12

Short - patient may die within 12-24 hours or recover rapidly following appropriate anti-shock therapy

Question 13

What are the warning signs of shock of DSS?

Answer 13

• Acute abdominal pain frequent complaint shortly before onset of shock
• Restlessness/lethargy
• Cold extremities
• Skin congestion
• Oliguria

Question 14

How are dengue cases classified according to the 2009 WHO criteria?

Answer 14

According to severity
- Dengue without warning signs: non-severe
- Dengue with warning signs: deterioration, abdominal pain/tenderness, persistent vomiting, fluid accumulation, mucosal bleed, lethargy, liver enlargement, increasing haematocrit, rapidly decreasing platelet count (needs strict observation and intervention)

Question 15

How does severe plasma leakage occur in DSS?

Answer 15

Acute increase in vascular permeability (major pathophysiological abnormality)

Question 16

How to manage DSS?

Answer 16

• Basic principle: correction of plasma leakage by volume replacement (infusion of plasma, plasma expander or electrolyte solution)
• Salicylates should be avoided as it causes bleeding -> paracetamol preferred

Question 17

What is the antibody response in the first infection?

Answer 17

Primary-type antibody response
- Initialy IgM (antibody produced against type-specific antigenic determinants)
- IgG antibody follows (neutralising antibody)
- Patient immune to infecting dengue serotype and partial protection against other serotypes

Question 18

What is the antibody response in the second infection?

Answer 18

Secondary-type antibody response
- IgG antibody predominant (antibody produced against group/subgroup specific antigenic determinants and non-neutralising, infection-enhancing)
- Patient protected against clinical disease on subsequent infections

Question 19

Describe the pathogenesis

Answer 19

1. Dengue virus deposited in skin by biting mosquito vector
2. Virus replicates initially at site of infection and in local lymphatic tissue
3. Viraemia within a few days
4. Virus replicates in mononuclear phagocytes (monocytes, macrophages, histiocytes, Kupffer cells)
5. Viral virulence (strains vary in pathogenic potential and severe complications caused by virulent strains) OR Immune enhancement involving infection-enhancing antibodies

Question 20

Describe immune enhancement in second infection group

Answer 20

• Non-neutralising enhancing antibodies form immune complexes with replicating virus
• Immune complexes attach to Fc receptors on mononuclear phagocytes
• Immune complexes internalised (virus continues to replicate in infected cell and mobile cells spread infection)
• Infection activates mononuclear phagocyte, releasing factors responsible for increased vascular permeability and disorder in haemostasis
• Enzymes cleave C3 to release anaphylatoxins, leukocyte thromboplastin causing haemorrhage, activation of complement system

Question 21

How do infants have high risk of developing DSS?

Answer 21

• Infants in first 6 months protected by maternal dengue neutralising antibodies
• As maternal IgG degrades, dengue neutralising antibodies decrease to below protective level
• Infant exposed to dengue virus at this stage have high risk

Question 22

What is the vector?

Answer 22

Aedes aegypti (main)
Aedes albopictus

Question 23

What is the reservoir?

Answer 23

Human (main)
Monkey may be jungle reservoir

Question 24

How is it transmitted?

Answer 24

Human-mosquito-human

Question 25

How to diagnose?

Answer 25

* Serological tests (IgM&IgG ELISA, NS1 antigen ELISA, POC test, haemagglutination inhibition test) * RT-PCR serum * Isolate virus (live mosquitoes, cell cultures)

Question 26

How to prevent and control?

Answer 26

Using live attenuated tetravalent dengue virus vaccines Control vector mosquitoes (reduce source, adulticiding, health education, law enforcement, *Wolbachia* field trials)