For developing severe dengue[7]
Age - 95% of severe dengue occurs in the those aged under 15 years.
Repeated dengue infections - infection with a secondary serotype is a risk factor for the development of severe disease[8].
Genetic factors - disease severity and outcome appear related to variation at multiple gene loci involved in immune response[9].
Viral genotypes - some strains may be more virulent.
Nutritional status - malnourished children are less likely to develop severe dengue than well nourished children, due to impaired cellular immunity but, where they do, the disease is more likely to be severe.
Pathophysiology[10]
Infection by any of the four serotypes may range from asymptomatic to life-threatening. The pathological effects are immune-mediated[11]. The development of severe disease seems to involve a complex interplay of host immunity and genetic predisposition combined with certain viral virulence factors[11].
Patients become infected once bitten by infected mosquitoes.
The virus passes to lymph nodes and replicates, mainly in monocytes and macrophages. It then spreads to the circulation and other tissues.
Incubation period is 2-7 days.
Initial immune activation leads to a flu-like illness of varying severity (dengue and severe dengue can be very similar at the start of the illness).
There is a tendency to haemorrhage associated with severe thrombocytopenia: this can also be seen in non-severe dengue.
Proliferation of T cells and the production of cytokines may lead to vascular endothelial cell dysfunction and to plasma leakage. When severe this capillary leak characterises severe dengue. It causes an increase in haematocrit, hypoalbuminaemia, pleural effusions and ascites.
In severe cases there may be multiple organ failure.
Multiple organ dysfunction can also result from direct viral damage to organs, particularly heart, brain and liver.
Recovery from infection by one dengue serotype provides full lifelong immunity only against that serotype. Cross-immunity to the other serotypes is partial and temporary.
Subsequent infections by other serotypes increase the risk of developing severe dengue.
Infants can develop severe dengue infection during their primary infection due to transplacental transfer of maternal antibodies to a different serotype from an immune mother. These amplify the infant's immune response to the primary infection.
The pathogenesis of severe dengue is thought to be immune-mediated. Recent evidence suggests cross-reactive high pro-inflammatory cytokine producing T cells predominate in severe dengue. Studies also suggests that there may be a genetic susceptibility to severe disease[11].
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