Dengue Flashcards
What family does it belong to?
Flavivirus
How many serotypes are there?
4
Characteristics
Shape, envelope?, genome
Spherical, enveloped, single-stranded RNA genome
What antigenic determinants does the envelope glycoprotein contain?
Group, subgroup, type specific
What are the 3 manifestations of symptomatic infection?
- Undifferentiated fever (infants and young children)
- Dengue fever
- Dengue haemorrhagic fever/Dengue shock syndrome
Describe the infection and serotype linkage
- First infection with any serotype
- Subsequent infection with serotype different from that of first infection
What does dengue fever cause?
- Abrupt onset of high fever
- Severe headache
- Pain behind eyes
- Muscle and joint pains
- Rash with islands of sparing
What does Dengue Haemorrhagic Fever cause?
- Ascites (acute abdominal pain)
- Haemorrhagic manifestations, including at least a positive tourniquet test (petechia, purpura, ecchymosis, epistaxis, gum bleeding, haematemesis, melaena)
- Lab
What is the clinical criteria of Dengue Shock Syndrome?
- 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
What is the laboratory criteria of Dengue Haemorrhagic Fever/Shock Syndrome?
- Thrombocytopaenia (100000/mm3 or less)
- Haemoconcentration: haematocrit increased by 20% or more of recovery value
- Raised ALT/AST enzymes
When does Dengue Shock Syndrome occur?
At time of/shortly after fall in temperature between day 3 and 7 of disease
How long is the duration of shock of DSS?
will pt die or recover :0
Short - patient may die within 12-24 hours or recover rapidly following appropriate anti-shock therapy
What are the warning signs of shock of DSS?
- Acute abdominal pain frequent complaint shortly before onset of shock
- Restlessness/lethargy
- Cold extremities
- Skin congestion
- Oliguria
How are dengue cases classified according to the 2009 WHO criteria?
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)
How does severe plasma leakage occur in DSS?
Acute increase in vascular permeability (major pathophysiological abnormality)
How to manage DSS?
- 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
What is the antibody response in the first infection?
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
What is the antibody response in the second infection?
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
Describe the pathogenesis
- Dengue virus deposited in skin by biting mosquito vector
- Virus replicates initially at site of infection and in local lymphatic tissue
- Viraemia within a few days
- Virus replicates in mononuclear phagocytes (monocytes, macrophages, histiocytes, Kupffer cells)
- Viral virulence (strains vary in pathogenic potential and severe complications caused by virulent strains) OR Immune enhancement involving infection-enhancing antibodies
Describe immune enhancement in second infection group
- 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
How do infants have high risk of developing DSS?
- 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
What is the vector?
Aedes aegypti (main)
Aedes albopictus
What is the reservoir?
Human (main)
Monkey may be jungle reservoir
How is it transmitted?
Human-mosquito-human
How to diagnose?
- Serological tests (IgM&IgG ELISA, NS1 antigen ELISA, POC test, haemagglutination inhibition test)
- RT-PCR serum
- Isolate virus (live mosquitoes, cell cultures)
How to prevent and control?
Using live attenuated tetravalent dengue virus vaccines
Control vector mosquitoes (reduce source, adulticiding, health education, law enforcement, Wolbachia field trials)
