Knowledge gaps in the epidemiology of severe dengue impede vaccine evaluation

The most severe consequences of dengue virus infection include shock, haemorrhage, and major organ failure; however, the frequency of these manifestations varies, and the relative contribution of pre-existing anti-dengue virus antibodies, virus characteristics, and host factors (including age and comorbidities) are not well understood. Reliable characterisation of the epidemiology of severe dengue first depends on the use of consistent definitions of disease severity. As vaccine trials have shown, severe dengue is a crucial interventional endpoint, yet the infrequency of its occurrence necessitates the inclusion of thousands of study participants to appropriately compare its frequency among participants who have and have not been vaccinated. Hospital admission is frequently used as a proxy for severe dengue; however, lack of specificity and variability in clinical practices limit the reliability of this approach. Although previous infection with a dengue virus is the best characterised risk factor for developing severe dengue, the influence of the timing between dengue virus infections and the sequence of dengue virus infections on disease severity is only beginning to be elucidated. To improve our understanding of the diverse factors that shape the clinical spectrum of disease resulting from dengue virus infection, prospective, community-based and clinic-based immunological, virological, genetic, and clinical studies across a range of ages and geographical regions are needed.

Automated summary

The frequency and contributing factors of severe dengue virus infection are not well understood. Consistent definitions of disease severity are needed for reliable characterization of severe dengue epidemiology. Hospital admission, although used as a proxy, lacks specificity and variability in clinical practices. Previous infection with dengue virus is a known risk factor for severe dengue, but the timing and sequence of infections on disease severity is only beginning to be understood. Comprehensive studies across various age groups and geographical regions are needed to improve our understanding of the clinical spectrum of disease resulting from dengue virus infection.