Dengue

Question 1

Dengue virus characteristics

Answer 1

RNA single stranded virus with four genetically distinct serotypes

Question 2

Dengue vectors

Answer 2

Aedes agypti and aedes albopictus (day biting)

Question 3

Dengue clinical features

Answer 3

Fever, myalgia, retro-orbital headache, joint pain
Maculopapular rash
Petechial rash on hands and feet after 4 days
White spots in a sea of red during recovery

Question 4

Dengue - geographical distribution

Answer 4

South America, Asia, Africa

Question 5

Dengue warning signs

Answer 5

Severe abdominal pain
Persistent vomiting
Liver enlargement
ALT >1000
Fluid accumulation (plasma leakage)
Lethargy
Sudden drop in platelet count
Rising haematocrit
Narrow pulse pressure

Question 6

The role of NS1 protein in dengue

Answer 6

1. Glycoprotein which stabilises the viral replication system
2. Disrupts endothelial dysfunction
3. Activation of Toll-like receptor 4 which triggers cascade of complement

Question 7

Host factors in the severity of dengue

Answer 7

• Children more likely to get plasma leakage
• Adults more like to have bleeding and organ damage

Other at risk characteristics:
- Children
- Pregnant women
- > 60 years
- DM and HTN

Question 8

Viral factors affecting disease severity in dengue

Answer 8

• High viral load
• High NS1
• Genotype

Question 9

Antibody dependent enhancement in dengue

Answer 9

More severe dengue in subsequent episodes because:
1. Primary dengue infection - body makes antibodies against that particular serotype
2. Secondary dengue infection - the body partially recognises it, and antibodies bind but are not completely effective at neutralising it
3. The antibodies stick to the virus forming a protective coat, allowing it to get a “free pass” into immune cells
4. As a result there is increased viral replication

Question 10

Dengue management

Answer 10

Supportive therapy
Careful fluid balance
Often platelet transfusion/antivirals are not helpful

Question 11

Dengue diagnostics

Answer 11

1st week of illness:
Identification of viral RNA and NS1 Ag using ELISA

End of 1st week:
IgM, IgG
Rapid tests, often combining NS1 detection with Ab test

Question 12

Challenges in dengue diagnostics

Answer 12

PCR: need centralised lab, expensive, narrow window
NS1: Poor sensitivity (DENV 2)
Cross reactivity with other flaviviruses

Question 13

Dengue prevention measures

Answer 13

1. Vaccination - Dengvaxia - tetravalent live-attenuated and Takeda Q denga.
   Challenge in covering multiple serotypes, and cause more severe disease in those who are infection naive.
2. Vector control - insecticides and avoiding standing water
3. Wolbachia program

Question 14

What are the phases of disease in dengue?

Answer 14

1. Febrile phase
2. Critical phase
3. Recovery phase

Question 15

What are the criteria for severe disease in dengue?

Answer 15

• Severe haemorrhage
• Severe plasma leakage
• Severe organ involvement (AST/ALT>1000)

Question 16

4 risk factors for critical disease in dengue

Answer 16

1. Pregnancy
2. Age >60
3. Immunocompromised
4. Over/under nutrition